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Live birth rates and birth outcomes by diagnosis using linked cycles from the SART CORS database
Abstract
This study uses linked cycles of assisted reproductive technology (ART) to examine cumulative live birth rates, birthweight, and length of gestation by diagnostic category.
We studied 145,660 women with 235,985 ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System during 2004-2010. ART cycles were linked to individual women by name, date of birth, social security number, partner's name, and sequence of ART treatments. The study population included the first four autologous oocyte cycles for women with a single diagnosis of male factor, endometriosis, ovulation disorders, diminished ovarian reserve, or unexplained infertility. Live birth rates were calculated per cycle, per cycle number (1-4), and cumulatively. Birthweight and length of gestation were calculated for singleton births.
Within each diagnosis, live birth rates were highest in the first cycle and declined with successive cycles. Women with diminished ovarian reserve had the lowest live birth rate (cumulative rate of 28.3 %); the live birth rate for the other diagnoses were very similar (cumulative rates from 62.1 % to 65.7 %). Singleton birthweights and lengths of gestation did not differ substantially across diagnoses, ranging from 3,112 to 3,286 g and 265 to 270 days, respectively. These outcomes were comparable with national averages for singleton births in the United States (3,296 g and 271 days).
Women with the diagnosis of diminished ovarian reserve had substantially lower live birth rates. However, singleton birthweights and lengths of gestation outcomes were similar across all other diagnoses.
... 13 Furthermore, the same review suggests that patients with endometriosis have a reduced ovarian reserve, once fewer oocytes are retrieved from women in this group. Since a poor ovarian reserve is associated with poor reproductive outcomes, 16,17 it is possible that the differences in the ovarian reserve, and not endometriosis itself, might be the cause of the heterogeneity observed in the studies published so far. 13 Conclusions Women diagnosed with endometriosis are more likely to have a poor ovarian reserve; however, their chance of conceiving by IVF/ICSI is similar to the one observed in patients without endometriosis and with a comparable ovarian reserve. ...
... [27][28][29] We believe that the difference among studies might be explained by the reduced ovarian reserve associated with endometriosis, as this reduction is related to poor assisted reproduction outcomes. 16 A recent and large observational study 16 examined data from more than 140,000 women with a single diagnosis of infertility; those with more than one cause were excluded from the analysis. Since this study considered that a reduced ovarian reserve was one of the causes of infertility, women with both endometriosis and a reduced ovarian reserve were not analyzed. ...
... very similar to those observed in couples with only male factor (42.7%), with only ovulatory dysfunction (44.1%), and those with unexplained infertility (42%); however, all of these rates were much higher than those observed in couples in which the woman had a reduced ovarian reserve and no other cause of subfertility was detected (18.9%). 16 Since women with endometriosis are more likely to have a reduced ovarian reserve, there is a reasonable chance to observe worse reproductive outcomes in women with endometriosis by including all women without controlling for this confounding factor. ...
Purpose
To evaluate whether women with endometriosis have different ovarian reserves and reproductive outcomes when compared with women without this diagnosis undergoing in vitro fertilization/intracytoplasmic sperm injection ( IVF/ ICSI), and to compare the reproductive outcomes between women with and without the diagnosis considering the ovarian reserve assessed by antral follicle count ( AFC ).
Methods
This retrospective cohort study evaluated all women who underwent IVF/ ICSI in a university hospital in Brazil between January 2011 and December 2012. All patients were followed up until a negative pregnancy test or until the end of the pregnancy. The primary outcomes assessed were number of retrieved oocytes and live birth. Women were divided into two groups according to the diagnosis of endometriosis, and each group was divided again into a group that had AFC 6 (poor ovarian reserve) and another that had AFC 7 (normal ovarian reserve). Continuous variables with normal distribution were compared using unpaired t-test, and those without normal distribution, using Mann-Whitney test. Binary data were compared using either Fisher's exact test or Chi-square ⁽²⁾ test. The significance level was set as p < 0.05.
Results
787 women underwent IVF/ICSI (241 of which had endometriosis). Although the mean age has been similar between women with and without the diagnosis of endometriosis (33.8 4 versus 33.7 4.4 years, respectively), poor ovarian reserves were much more common in women with endometriosis (39.8 versus 22.7%). The chance of achieving live birth was similar between women with the diagnosis of endometriosis and those without it (19.1 versus 22.5%), and also when considering only women with a poor ovarian reserve (9.4 versus 8.9%) and only those with a normal ovarian reserve (25.5 versus 26.5%).
Conclusions
Women diagnosed with endometriosis are more likely to have a poor ovarian reserve; however, their chance of conceiving by IVF/ICSI is similar to the one observed in patients without endometriosis and with a comparable ovarian reserve.
... After the birth of the world's first IVF baby in the UK, Louise Brown (Steptoe and Edwards, 1978), and despite numerous advances in the field of reproductive medicine, the likelihood of achieving a live birth in couples undergoing assisted reproduction techniques remains low, ranging from 30-35% in young patients to less than 5-8% in patients older than 41-42 years of age (Gunby et al., 2011;Stern et al., 2013). A growing body of evidence suggests that the dramatic decline in IVF success rates with advanced female age is mainly caused by embryonic aneuploidy (Hardarson et al., 2008;Harton et al., 2013;Kroon et al., 2011;Munne et al., 1995). ...
... After the birth of the world's first IVF baby in the UK, Louise Brown (Steptoe and Edwards, 1978), and despite numerous advances in the field of reproductive medicine, the likelihood of achieving a live birth in couples undergoing assisted reproduction techniques remains low, ranging from 30-35% in young patients to less than 5-8% in patients older than 41-42 years of age (Gunby et al., 2011;Stern et al., 2013). A growing body of evidence suggests that the dramatic decline in IVF success rates with advanced female age is mainly caused by embryonic aneuploidy (Hardarson et al., 2008;Harton et al., 2013;Kroon et al., 2011;Munne et al., 1995). ...
Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to decreased implantation rates, IVF cycle failure and early pregnancy loss. Preimplantation genetic screening (PGS) selects the most competent (euploid) embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS-v1) significantly lowers live birth rates and is not recommended for use. Comprehensive chromosome screening technology, which assesses the whole chromosome complement, can be achieved using different genetic platforms. Whether PGS using comprehensive chromosome screening after blastocyst biopsy (PGS-v2) improves IVF outcomes remains to be determined. A systematic review of randomized controlled trials was conducted on PGS-v2. Three trials met full inclusion criteria, comparing PGS-v2 and routine IVF care. PGS-v2 is associated with higher clinical implantation rates, and higher ongoing pregnancy rates when the same number of embryos is transferred in both PGS and control groups. Additionally, PGS-v2 improves embryo selection for elective single embryo, maintaining the same ongoing pregnancy rates between PGS and control groups, while sharply decreasing multiple pregnancy rates. These results stem from good-prognosis patients undergoing IVF. Whether these findings can be extrapolated to poor-prognosis patients with decreased ovarian reserve remains to be determined.
... Previous research found that female obesity adversely affected the CLBR in their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles [11]. Women with diminished ovarian reserves had substantially lower live birth rates [12], and the anti-Müllerian hormone (AMH) levels, the basal follicle-stimulating hormone (FSH) levels, and AFC can be used as the indicators for ovarian reserve function [13][14][15]. There are also studies that found an additional predictor of the CLBR was the number of retrieved oocytes [16]. ...
The cumulative live birth rate (CLBR) can better reflect the overall treatment effect by successive treatments, and continuous rather than categorical variables as exposure variables can increase the statistical power in detecting the potential correlation. Therefore, the dose–response relationships might find an optimal dose for the better CLBR, offering evidence-based references for clinicians. To determine the dose–response relationships of the factors and the optimal ranges of the factors in assisted reproductive technology (ART) associated with a higher CLBR, this study retrospectively analyzed 16,583 patients undergoing the first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) from January 2017 to January 2019. Our study demonstrated the optimal ranges of age with a higher CLBR were under 32.10 years. We estimated the CLBR tends to increase with increased levels of AMH at AMH levels below 1.482 ng/mL, and the CLBR reaches a slightly high level at AMH levels in the range from 2.58–4.18 ng/mL. The optimal ranges of basal FSH with a higher CLBR were less than 9.13 IU. When the number of cryopreserved embryos was above 1.055 and the number of total transferred embryos was 2, the CLBR was significantly higher. In conclusion, there is a non-linear dose–response relationship between the CLBR with age, AMH, basal FSH, and the number of cryopreserved embryos and total transferred embryos. We proposed the optimal ranges of the five factors that were correlated with a higher CLBR in the first oocyte retrieval cycle, which may help consultation at IVF clinics.
... Хоча під час ДРТ може бути отримана велика кількість ооцитів, є побоювання, що якість і зрілість цих яйцеклітин будуть порушені [2][3][4][5][6][7][8][9]. Незважаючи на все це, рівень живонародження після ДРТ у жінок із СПКЯ зіставний з показниками у жінок з ендометріозом, нез'ясованим безпліддям або безпліддям з чоловічим фактором [10,11]. ...
РЕЗЮМЕ. Орієнтовно 80–90 % жінок із ановуляцією, які звертаються в клініку, мають СПКЯ. За різними даними, хронічний ендометрит розпізнається від дуже низької до дуже високої частоти, зокрема, у 2,8 % – 67,6 % пацієнтів із безпліддям та невдалою імплантацією, що обґрунтовує доцільність вивчення особливостей безпліддя на фоні СПКЯ та хронічного ендометриту. Мета – вивчити особливості оогенезу, запліднення, настання вагітностей в програмах ЕКЗ у пацієнток із ендокринним безпліддям на фоні СПКЯ та на тлі коморбідності синдрому полікістозних яєчників і хронічного ендометриту. Матеріали та методи. Зроблено ретроспективний аналіз медичних карт 110 жінок із ендокринним безпліддям на тлі синдрому полікістозних яєчників та коморбідністю СПКЯ і хронічного ендрометриту, а також 30 жінок, які склали контрольну групу. Пацієнтки були поділені на 3 групи. Першу дослідну групу склали 52 жінки з ендокринним безпліддям на тлі СПКЯ, другу – 58 жінок із безпліддям на фоні СПКЯ та хронічного ендометриту (в цю групу були включені пацієнтки із невдалими спробами ЕКЗ та/або вагітністю, яка перервалася на ранніх термінах), а також 30 пацієнток з безпліддям, пов’язаним із чоловічим фактором, які склали групу порівняння (контроль). Нами проведено порівняльний аналіз загальноклінічних показників пацієнток з ендокринним безпліддям на тлі СПКЯ та коморбідністю СПКЯ і хронічного ендометриту. Проаналізовано отримані результати ефективності коротких протоколів ЕКЗ з антагоністом ГнРГ у цих пацієнток, такі як характеристика фолікулогенезу, отриманих ооцитів та ембріонів, клінічні результати настання вагітності та пологів. Результати. На основі проведеного ретроспективного аналізу оперативних втручань у пацієнток із коморбідністю СПКЯ та хронічного ендометриту виявлено у більшої кількісті жінок вишкрібання стінок порожнини матки у 24,14 % та ВМС у 20,69 % в анамнезі, що могло бути одним із причинних факторів виникнення хронічного ендометриту. При оцінці результатів стимуляції суперовуляції виявлено більшу тривалість днів стимуляції, вищу загальну дозу гонадотропінів, меншу кількість виходу бластоцист, а також нижчий відсоток настання вагітності. Це дозволило в подальшому визначити пріоритетні методи підготовки пацієнток дослідних груп до кріопротоколу з метою реалізації їх репродуктивної функції. Висновки. У пацієнток із ендокринним безпліддям на фоні коморбідності СПКЯ і хронічного ендометриту, у порівнянні з групою жінок із безпліддям на тлі СПКЯ, для стимуляції суперовуляції необхідна вища загальна доза рФСГ, тривалість введення антагоніста ГнРГ, тривалість КОС та достовірно нижча кількість отриманих ооцитів, запліднених яйцеклітин та бластоцист, а також нижчий відсоток настання вагітності.
... [21] Among studies that investigated separate effects of infertility etiologies on pregnancy outcomes, Stern et al. evaluated 235,985 ART cycles in 145,660 infertile women, and as in our study, no difference was found regarding birth weights and pregnancy durations among patients with endometriosis, male factor infertility, low ovarian reserve, unexplained infertility and anovulation. [22] Hayashi et al. compared ART techniques (ovulation stimulation medications n=4111; IUI n= 2351 and IVF-ET n=4570) to spontaneous pregnancies, and higher rates of PTD and low birth weight were observed in infertile patients independently of the ART technique. [23] Studies on sub-fertile women have shown that patients are exposed to pregnancy risks even without receiving any treatment. ...
Objective: Pregnancies after in vitro fertilization (IVF) are associated with a less favorable outcome compared to natural conception as consistently shown in various studies. However, etiologic factors behind this issue remain to be elucidated. We aimed to demonstrate whether the etiology of infertility has a role on poor pregnancy outcomes in IVF pregnancies. Methods: In this retrospective case control study; IVF and spontaneous singleton pregnancies were investigated. The infertile patients were divided into six groups according to the etiology of their infertility (anovulation, male factor, tubal factor, endometriosis, unexplained infertility and poor ovarian reserve). The incidence of preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, preterm birth and birth weight discrepancies was examined between the groups and subgroups. After adjusting the confounding variables for each infertility subgroup such as demographic data, embryo stage in transfer (blastocyst against cleavage stage) and fresh and frozen embryo transfer status, the effect on pregnancy outcomes was investigated using multinomial logistic regression analysis. Results: The study included 934 patients in the IVF group and 1009 patients in the control group. While adverse pregnancy outcomes were more frequent in the general infertility group in comparison to the control group, after elimination of the confounding variables, the direct effect of the etiology of infertility on these outcomes could not be shown. Conclusion: In the IVF pregnancies, most of the increased risk of poor pregnancy outcomes appeared to be explained by maternal characteristics (such as age, body mass index) and by treatment protocols rather than infertility etiology. Physicians should consider these risks while counselling patients.
... The assisted reproduction, namely test-tube baby technology, is often the final resolution to against infertility in many cases. However, the success rate of conventional IVF procedure is merely 30-35% in average, and could be even lower to 5-8% in females over age 40 [11][12][13][14][15][16]. Scientific researches has revealed that embryo chromosomal abnormality is one of major causes of IVF failure [17][18][19][20]. ...
Next Generation Sequencing (NGS) is a powerful tool getting into the field of clinical examination. Its preliminary application in pre-implantation comprehensive chromosomal screening (PCCS) of assisted reproduction (test-tube baby) has shown encouraging outcomes that improves the success rate of in vitro fertilization. However, the conventional NGS library construction is time consuming. In addition with the whole genome amplification (WGA) procedure in prior, makes the single cell NGS assay hardly be accomplished within an adequately short turnover time in supporting fresh embryo implantation. In this work, we established a concise single cell sequencing protocol, ChromInst, in which the single cell WGA and NGS library construction were integrated into a two-step PCR procedure of ~ 2.5hours reaction time. We then validated the feasibility of ChromInst for overnight PCCS assay by examining 14 voluntary donated embryo biopsy samples in a single sequencing run of Miseq with merely 13M reads production. The good compatibility of ChromInst with the restriction of Illumina sequencing technique along with the good library yield uniformity resulted superior data usage efficiency and reads distribution evenness that ensures precisely distinguish of 6 normal embryos from 8 abnormal one with variable chromosomal aneuploidy. The superior succinctness and effectiveness of this protocol permits its utilization in other time limited single cell NGS applications.
... It is improbable that these etiological differences biased the primary outcome of our study, since the North American (SART) database report examining nearly a quarter of a million IVF cycles has concluded that IVF live birth rates are not significantly different for couples with male factor, ovulatory dysfunction, or endometriosis related infertility, with success rates only being inferior in those women with diminished ovarian reserve. 42 As the Menevit and control groups had comparable ovarian reserve status (serum AMH and number of oocytes retrieved; Table 1 and 2), the differences in etiology between these two comparator groups are very unlikely to account for the observed differences in live birth outcomes. In addition, while ICSI was more commonly used in the Menevit group than the controls, reflecting the higher incidence of male factor infertility, this difference in fertilization technique is also unlikely to positively bias pregnancy outcomes in the Menevit cohort as live birth rates tend to be marginally inferior in ICSI cycles than IVF, even in nonmale factor infertility patients. ...
Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking "general health" supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01-2.45, P= 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18-6.28; P= 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75-2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.
... Since each woman could have several ART treatments, the observation unit was the embryo transfer. [39][40][41] According to the outcome of CM, each woman with hyperthyroidism or hypothyroidism could have had several childbirths during the study period and the observational unit for examining the risk of CMs was the live-born child. ...
Purpose:
Women with thyroid disorders may have increased infertility and poor reproductive outcomes, but it is unclear if assisted reproductive technology (ART) is effective in this population. The aim of this study was to examine the chance of a pregnancy (biochemical and clinical), and a live birth after ART, in women with thyroid disorders undergoing ART treatment, compared to women without thyroid disorders. Among live-born children, we assessed the risk of congenital malformations.
Patients and methods:
In a nationwide cohort study of all women undergoing ART treatments in Denmark from 1 January 1994 throughout June 2017, we calculated the chance of a pregnancy and a live birth after embryo transfer. Women with thyroid disorders were stratified into two groups: those diagnosed with hypothyroid or hyperthyroid disorders. The adjusted OR (aOR) of a biochemical and a clinical pregnancy, a live born child and a congenital malformation was computed using multilevel logistic regression models.
Results:
In total, 199,674 embryo transfers were included in 2,101 women with thyroid disorders and in 65,526 women without thyroid disorders. The chance of a biochemical pregnancy was significantly reduced in women with hyperthyroidism (aOR=0.80, 95% CI 0.69-0.93), and the aOR of a live birth was 0.86, 95% CI 0.76-0.98. The aOR for a live birth in women with hypothyroidism was 1.03 (95% CI 0.94-1.12). Children of women with hypothyroidism, who were conceived after ART treatment, had a significantly increased risk of any congenital malformation (aOR=1.46 [95% CI 1.07-2.00]).
Conclusion:
Women with hyperthyroidism receiving ART treatment had a decreased chance of a live birth per embryo transfer compared to women without thyroid disorders. Women with hypothyroidism did not have a decreased chance of a live birth but their offspring had an increased risk of congenital malformation.
... Advanced female age is related to a reduced natural fertility and poor ART outcomes, and a high FOR is related to successful ART outcomes. Data on 145,660 ART cycles reported to the American Society of Reproductive Medicine in 2012 indicated that low FOR was responsible for about 16% of unsuccessful ARTs, and the rates of live births after ART were significantly lower in women with low FOR than those with male factor infertility, endometriosis, ovulatory disorders, and idiopathic dysfunction 4 . Moreover, about 41% of the women who had low FOR were less than 35 years-old 4 . ...
To investigate the relationship of birth weight (BW) of females born at full term with functional ovarian reserve (FOR) during menacme, based on serum level of anti-Müllerian hormone (AMH), among women who were 34–35 years old. This prospective birth cohort study assessed all women who were born in Ribeirão Preto City, State of São Paulo (Brazil) between June 1, 1978 and May 31, 1979. The primary endpoint was serum AMH, a marker of FOR, and its correlation with the BW of females classified as small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational (LGA). We included 274 women in this study, 19 were SGA, 238 were AGA, and 17 were LGA. The average of AMH concentration was not significantly different (p = 0.11) among women in the SGA group (2.14 ng/mL), AGA group (2.13 ng/mL), and LGA group (2.57 ng/mL). An analysis of variance indicated that the three groups also had no significant differences in the percentage of women who had adequate AMH levels (1 ng/mL; p = 0.11). There were no significant differences in the serum concentrations of AMH among 34 and 35 year-old women who were born at full term and classified as SGA, AGA, and LGA. Our sample size allowed detection of major differences between these groups (effect size of 0.8). Association of birth weight of females born at full term with functional ovarian reserve during menacme estimated by serum concentration of anti-Müllerian hormone.
... The electronic search strategy identified 3925 records, and 2794 studies were identified following the removal of duplicates. Following title and abstract screen, 117 studies were included for full text review, and 33 studies (sample size, n = 3 280 488) were included in the metaanalysis ( Fig. 1) (Kortelahti et al., 2003;Omland et al., 2005;Brosens et al., 2007;Fernando et al., 2009;Hadfield et al., 2009;Healy et al., 2010;Kuivasaari-Pirinen et al., 2012;Takemura et al., 2013;Aris, 2014;Conti et al., 2014;Mekaru et al., 2014;Rombauts et al., 2014;Baggio et al., 2015;Lin et al., 2015;Messerlian et al., 2015;Stern et al., 2013Stern et al., , 2015Benaglia et al., 2012Benaglia et al., , 2016Exacoustos et al., 2016;Fujii et al., 2016;Guo et al., 2016;Harada et al., 2016;Jacques et al., 2016;Morassutto et al., 2016;Berlac et al., 2017;Glavind et al., 2017;Li et al., 2017;Mannini et al., 2017;Pan et al., 2017;Saraswat et al., 2017;Tzur et al., 2018;Chen et al., 2018). ...
Study question:
How is endometriosis associated with adverse maternal, fetal and neonatal outcomes of pregnancy?
Summary answer:
Women with endometriosis are at elevated risk for serious and important adverse maternal (pre-eclampsia, gestational diabetes, placenta praevia and Cesarean section) and fetal or neonatal outcomes (preterm birth, PPROM, small for gestational age, stillbirth and neonatal death).
What is known already:
A number of studies have shown an association between endometriosis and certain adverse maternal and fetal outcomes, but the results have been conflicting with potential for confounding by the use of assisted reproductive technology.
Study design, size, duration:
A systematic review and meta-analysis of observational studies (1 January 1990-31 December 2017) that evaluated the effect of endometriosis on maternal, fetal and neonatal outcomes was conducted.
Participants/materials, setting, methods:
Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies; included women greater than 20 weeks gestational age with endometriosis; included a control group of gravid women without endometriosis; and, reported at least one of the outcomes of interest. Each study was reviewed for inclusion, data were extracted and risk of bias was assessed by two independent reviewers.
Main results and the role of chance:
The search strategy identified 33 studies (sample size, n = 3 280 488) for inclusion. Compared with women without endometriosis, women with endometriosis had higher odds of pre-eclampsia (odds ratio [OR] = 1.18 [1.01-1.39]), gestational hypertension and/or pre-eclampsia (OR = 1.21 [1.05-1.39]), gestational diabetes (OR = 1.26 [1.03-1.55]), gestational cholestasis (OR = 4.87 [1.85-12.83]), placenta praevia (OR = 3.31 [2.37, 4.63]), antepartum hemorrhage (OR = 1.69 [1.38-2.07]), antepartum hospital admissions (OR = 3.18 [2.60-3.87]), malpresentation (OR = 1.71 [1.34, 2.18]), labor dystocia (OR = 1.45 [1.04-2.01]) and cesarean section (OR = 1.86 [1.51-2.29]). Fetuses and neonates of women with endometriosis were also more likely to have preterm premature rupture of membranes (OR = 2.33 [1.39-3.90]), preterm birth (OR = 1.70 [1.40-2.06]), small for gestational age <10th% (OR = 1.28 [1.11-1.49]), NICU admission (OR = 1.39 [1.08-1.78]), stillbirth (OR = 1.29 [1.10, 1.52]) and neonatal death (MOR = 1.78 [1.46-2.16]). Among the subgroup of women who conceived spontaneously, endometriosis was found to be associated with placenta praevia, cesarean section, preterm birth and low birth weight. Among the subgroup of women who conceived with the use of assisted reproductive technology, endometriosis was found to be associated with placenta praevia and preterm birth.
Limitations, reasons for caution:
As with any systematic review, the review is limited by the quality of the included studies. The diagnosis for endometriosis and the selection of comparison groups were not uniform across studies. However, the effect of potential misclassification would be bias towards the null hypothesis.
Wider implications of the findings:
The association between endometriosis with the important and serious pregnancy outcomes observed in our meta-analysis, in particular stillbirth and neonatal death, is concerning and warrants further studies to elucidate the mechanisms for the observed findings.
Study funding/competing interest(s):
Dr Shifana Lalani is supported by a Physicians' Services Incorporated Foundation Research Grant, and Dr Innie Chen is supported by a University of Ottawa Clinical Research Chair in Reproductive Population Health and Health Services. Dr Singh declares conflicts of interests with Bayer, Abvie, Allergan and Cooper Surgical. All other authors have no conflicts of interests to declare.
Registration number:
PROSPERO CRD42015013911.
... However, more recent analyses have suggested that a diagnosis of endometriosis may be associated with comparable pregnancy outcomes compared to other infertility diagnostic groups. In a retrospective analysis of linked cycles from the SART database over a 7 year period, live birth rates were similar to other IVF diagnostic groups in both fresh and frozen cycles (4). However, this particular analysis reported on endometriosis as a single diagnosis. ...
Objective:
To assess the impact of endometriosis, alone or in combination with other infertility diagnoses, on IVF outcomes.
Design:
Population-based retrospective cohort study of cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.
Setting:
Not applicable.
Patient(s):
A total of 347,185 autologous fresh and frozen assisted reproductive technology cycles from the period 2008-2010.
Intervention(s):
None.
Main outcome measure(s):
Oocyte yield, implantation rate, live birth rate.
Result(s):
Although cycles of patients with endometriosis constituted 11% of the study sample, the majority (64%) reported a concomitant diagnosis, with male factor (42%), tubal factor (29%), and diminished ovarian reserve (22%) being the most common. Endometriosis, when isolated or with concomitant diagnoses, was associated with lower oocyte yield compared with those with unexplained infertility, tubal factor, and all other infertility diagnoses combined. Women with isolated endometriosis had similar or higher live birth rates compared with those in other diagnostic groups. However, women with endometriosis with concomitant diagnoses had lower implantation rates and live birth rates compared with unexplained infertility, tubal factor, and all other diagnostic groups.
Conclusion(s):
Endometriosis is associated with lower oocyte yield, lower implantation rates, and lower pregnancy rates after IVF. However, the association of endometriosis and IVF outcomes is confounded by other infertility diagnoses. Endometriosis, when associated with other alterations in the reproductive tract, has the lowest chance of live birth. In contrast, for the minority of women who have endometriosis in isolation, the live birth rate is similar or slightly higher compared with other infertility diagnoses.
... Whilst a high number of oocytes may be obtained during ART, there are concerns that the quality and maturity of these oocytes may be compromised [10][11][12][13][14][15][16][17] . Despite all of this, live birth rates after ART in women with PCOS seem to be comparable to women with other diagnoses, such as endometriosis, unexplained infertility or male factor infertility 18,19 . ...
Objectives:
To identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS).
Methods:
A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage.
Results:
We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS.
Conclusion:
There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto.
Resultados:
Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0,95 (IC 95%, 0,84-1,08)), o de embarazos confirmados ecográficamente (RR: 1,02 (IC 95%, 0,91-1,15)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1,28 (IC 95%, 1,01-1,63)) y de embarazos confirmados ecográficamente (RR: 1,26 (IC 95%, 1,04-1,53)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1,03 (IC 95%, 0,80-1,34)) y las tasas de embarazos confirmados ecográficamente (RR: 0,99 (IC 95%, 0.81-1,22)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0,54 (IC 95%, 0,39-0,77)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0,63 (IC 95%, 0,49-0,80)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes.
... Because each woman with UC or CD could have several ART treatments, the observation unit was the treatment cycle. [24][25][26] For the secondary outcomes (adverse birth outcomes), the exposed cohorts comprised all children who were conceived through ART treatment by women with UC or CD. Because each woman with UC or CD could have several births and each birth could include several children, the observation unit was the child. ...
Objective:
To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments.
Methods:
This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes.
Results:
The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62.
Conclusions:
Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.
... Cumulative live birth rates (CLBRs) following IVF have been reported mainly at a sub-national level (Elizur et al., 2006;Malizia et al., 2009;Ke et al., 2013;Vrtacnik et al., 2014). Although they have been reported at the national level in the USA (Luke et al., 2012;Stern et al., 2013) and Australia and New Zealand (Macaldowie et al., 2013) not all the reports have been able to generate figures for cumulative live birth after several complete IVF cycles. Until now, no studies have reported such rates for the UK (Johnson and Franklin, 2013). ...
Study question:
What is the chance of a live birth following one or more linked complete cycles of IVF (including ICSI)?
Summary answer:
The chance of a live birth after three complete cycles of IVF was 42.3% for treatment commencing from 1999 to 2007.
What is known already:
IVF success has generally been reported on the basis of live birth rates after a single episode of treatment resulting in the transfer of a fresh embryo. This fails to capture the real chance of having a baby after a number of complete cycles-each involving the replacement of fresh as well as frozen-thawed embryos.
Study design, size and duration:
Population-based observational cohort study of 178 898 women between 1992 and 2007.
Participants/materials, setting, methods:
Participants included all women who commenced IVF treatment at a licenced clinic in the UK as recorded in the Human Fertilisation and Embryology Authority (HFEA) national database. Exclusion criteria included women whose treatment involved donor insemination, egg donation, surrogacy and the transfer of more than three embryos. Cumulative rates of live birth, term (>37 weeks) singleton live birth, and multiple pregnancy were estimated for two time-periods, 1992-1998 and 1999-2007. Conservative estimates assumed that women who did not return for IVF would not have the outcome of interest while optimal estimates assumed that these women would have similar outcome rates to those who continued IVF.
Main results and the role of chance:
A total of 71 551 women commenced IVF treatment during 1992-1998 and an additional 107 347 during 1999-2007. After the third complete IVF cycle (defined as three fresh IVF treatments-including replacement of any surplus frozen-thawed embryos), the conservative CLBR in women who commenced IVF during 1992-1998 was 30.8% increasing to 42.3% during 1999-2007. The optimal CLBRs were 44.6 and 57.1%, respectively. After eight complete cycles the optimal CLBR was 82.4% in the latter time period. The conservative rate for multiple pregnancy per pregnant woman fell from 31.9% during the earlier time period to 26.2% during the latter.
Limitations and reason for caution:
Linkage of all IVF treatments to individual women was conducted. However, it was not possible to identify with certainty in all cases the episode of ovarian stimulation which generated some of the frozen embryos. Cumulative live birth rates could not be calculated for women who started treatment beyond 2007 as follow-up data were incomplete in some of them. Following a change in legislation in 2008, linked data were only made available for research in women who gave formal consent for this purpose. BMI and ethnicity could not be reported: these demographics are not recorded in the HFEA database.
Wider implications of the findings:
Our results demonstrate, at a national level, the chances of live birth in couples undergoing a number of complete (fresh and frozen) IVF cycles. They reflect improvements in reproductive technology and a more conservative embryo transfer policy. Although most couples in the UK still do not receive three complete IVF cycles; assuming no barriers to continuation of IVF treatment, around 83% of women receiving IVF would achieve a live birth by the eighth complete cycle, similar to the natural live birth rate in a non-contraception practising population. Our results support the call from NICE to develop consistent IVF policies based on three complete cycles.
Study funding/competing interests:
This work was funded by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office. S.B. reports grants from Chief Scientist Office Scotland during the conduct of the study. His institution has received support from Pharmaceutical companies (for educational seminars), which is not related to the submitted work. D.J.M., A.M. and A.J.L. have no conflicts of interest to declare.
... In several recent studies, ART was found to be effective in cases of endometriosis (10,11). Reverting to ART maximizes cycle fecundity, so it is a therapeutic option for many infertile women with endometriosis (9,12). ...
Objective:
To evaluate the impact of assisted reproduction technology (ART) on painful symptoms and quality of life (QoL) in women who have endometriosis as compared with disease-free women.
Design:
Prospective controlled, observational cohort study.
Setting:
University hospital.
Patient(s):
Two hundred and sixty-four matched-pairs of endometriosis and disease-free women undergoing ART.
Intervention(s):
Assessment of pain evolution using visual analogue scale (VAS) during ART; QoL assessment with the Fertility Quality of Life (FertiQoL) tool.
Main outcome measure(s):
VAS pain intensities relative to dysmenorrhea, dyspareunia, noncyclic chronic pelvic pain (NCCPP), gastrointestinal pain, lower urinary tract pain; trends for VAS change between postretrieval and baseline evaluation; FertiQoL score; and statistical analyses conducted using univariate and adjusted multiple linear regression models.
Result(s):
After excluding canceled cycles and patients lost to follow-up observation, 102 women with endometriosis and 104 disease-free women were retained for the study. The trends for VAS change between the postretrieval and baseline evaluations in the women with endometriosis compared with the disease-free women revealed a statistically significant pain decrease for dysmenorrhea (-1.35 ± 3.23 and 0.61 ± 4.00) and dyspareunia (-1.19 ± 2.58 and 0.14 ± 2.06). For NCCPP, gastrointestinal symptoms, and lower urinary tract symptoms, there were no statistically significant differences between the groups. After multiple linear regression, no worsening of pain was observed in the endometriosis group as compared with disease-free group. In addition subgroup analysis according to endometriosis phenotype failed to show any increase of pain. The quality of life in the endometriosis group was comparable to that of the disease-free group.
Conclusion(s):
Assisted reproduction technology did not exacerbate the symptoms of endometriosis or negatively impact QoL in women with endometriosis as compared with disease-free women.
... Some studies have used first live birth (Thurin-Kjellberg et al., 2009;Luke et al., 2012;Stern et al., 2013;Bodri et al., 2014) as the preferred numerator while others have included all live birth episodes from an index stimulation cycle (Li et al., 2014). There are advantages and disadvantages of both approaches. ...
Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing
use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen
embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having
a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the
most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension—time
for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is
generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this
statistic is calculated, reported and interpreted by stakeholders across the world.
... Endometriosis can cause adhesive disease that alters pelvic anatomy and may yield an inflammatory altered immune environment that has the potential to impact oocyte quality, embryogenesis, and implantation (3)(4)(5). The mechanism by which endometriosis contributes to infertility and its impact on fertility treatment success remain controversial (1,(6)(7)(8)(9)(10)(11)(12). Several studies, including systematic reviews and metaanalyses, have yielded conflicting results regarding the impact of endometriosis on ovarian reserve and IVF outcomes; several suggest comparable ART outcomes between women with and without endometriosis (8,9,13,14), whereas others suggest that the presence of endometriosis negatively affects ART success (6,8,9,12,13). ...
To assess endometriosis-associated infertility trends among assisted reproductive technology (ART) cycles, and to compare cancellation and hyperstimulation risks and pregnancy and live birth rates among women using ART for endometriosis-associated vs. male factor infertility.
Descriptive and multivariable analyses of Centers for Disease Control and Prevention (CDC) National ART Surveillance System data.
Fertility centers.
All reported fresh autologous ART cycles in the United States between 2000 and 2011 (n = 1,589,079).
None.
Oocyte yield, hyperstimulation, cancellation, implantation, pregnancy, live birth.
The absolute number of ART cycles with an endometriosis diagnosis fell in recent years, from 16,751 (2000) to 15,311 (2011); the percentage fell over time, from 17.0% (2000) to 9.6% (2011) of all cycles. Compared with male factor (n = 375,557), endometriosis-associated cycles (n = 112,475) yielded fewer oocytes (50.5% vs. 42.5% of cycles with only 0-10 oocytes retrieved), lower risk of hyperstimulation (1.1% vs. 1.3%, adjusted risk ratio [aRR] 0.82, 95% confidence interval [CI] 0.74-0.91), and an increased risk of cancellation (12.9% vs. 10.1%, aRR 1.30, 95% CI 1.25-1.35). Endometriosis was associated with a statistically decreased but likely clinically insignificant difference in the following outcomes: chance of pregnancy per transfer (43.7% vs. 44.8%, aRR 0.96, 95% CI 0.95-0.98) among couples who did not also have tubal factor infertility and live birth per transfer (37.2% vs. 37.6%, aRR 0.96, 95% CI 0.94-0.98).
The percentage of endometriosis-associated ART cycles has decreased over time. As compared with male factor infertility, endometriosis is associated with increased cancellation and decreased hyperstimulation risks. Despite decreased oocyte yield and higher medication dose, the difference in pregnancy and live birth rates may be of limited clinical significance, suggesting comparable pregnancy outcomes per transfer.
Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
... Diagnoses have also been shown to affect outcome in other studies (12,13). The current study adds to these prior studies by providing a direct diagnosis-specific comparison between ART and non-ART pregnancies as compared with fertile pregnancies. ...
To compare the risks for adverse pregnancy and birth outcomes by diagnoses with and without assisted reproductive technology (ART) treatment to non-ART pregnancies in fertile women.
Historical cohort of Massachusetts vital records linked to ART clinic data from Society for Assisted Reproductive Technology Clinic Outcome Reporting System.
Not applicable.
Diagnoses included male factor (ART only), endometriosis, ovulation disorders, tubal (ART only), and reproductive inflammatory disorders (non-ART only). Pregnancies resulting in singleton and twin live births from 2004 to 2008 were linked to hospital discharges in women who had ART treatment (n = 3,689), women with no ART treatment in the current pregnancy (n = 4,098), and non-ART pregnancies in fertile women (n = 297,987).
None.
Risks of gestational diabetes, prenatal hospitalizations, prematurity, low birth weight, and small for gestational age were modeled using multivariate logistic regression with fertile deliveries as the reference group adjusted for maternal age, race/ethnicity, education, chronic hypertension, diabetes mellitus, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals [CIs]).
Risk of prenatal hospital admissions was increased for endometriosis (ART: 1.97, 1.38-2.80; non-ART: 3.34, 2.59-4.31), ovulation disorders (ART: 2.31, 1.81-2.96; non-ART: 2.56, 2.05-3.21), tubal factor (ART: 1.51, 1.14-2.01), and reproductive inflammation (non-ART: 2.79, 2.47-3.15). Gestational diabetes was increased for women with ovulation disorders (ART: 2.17, 1.72-2.73; non-ART: 1.94, 1.52-2.48). Preterm delivery (AORs, 1.24-1.93) and low birth weight (AORs, 1.27-1.60) were increased in all groups except in endometriosis with ART.
The findings indicate substantial excess perinatal morbidities associated with underlying infertility-related diagnoses in both ART-treated and non-ART-treated women.
Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
... Sonographers should be aware that the threshold used for diagnosing HA should differ from that used to identify women at risk of an excessive response to controlled ovarian stimulation during assisted reproduction; a much lower threshold should be adopted to identify the latter. Women with a total antral follicle count (AFC) (considering both ovaries) of >20 have been shown to have a higher risk of developing OHSS 10,39 , while those with a reduced total AFC are known to be at risk of poor ovarian response 8 and have a reduced chance of pregnancy following assisted reproduction 40,41 . Thus, total AFC is frequently used for the individualization of controlled ovarian stimulation 39,42,43 . ...
... This analysis, developing a model predictive of live birth and multiple births based on U.S. national data, extends our prior studies of cumulative live-birth rates with ART treatment (12,13,(16)(17)(18). The prediction model presented here is intended for an individual considering ART and provides the probability of success over the course of the first three fresh autologous cycles and the first fresh donor cycle, as well as the effect of transferring one versus two embryos on the live-birth rate and the multiple birth rate. ...
Objective:
To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011.
Design:
Longitudinal cohort.
Setting:
Clinic-based data.
Patient(s):
288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle).
Intervention(s):
None.
Main outcome measure(s):
LBRs and MBRs modeled by woman's age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs) and 95% confidence intervals.
Result(s):
The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively).
Conclusion(s):
This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes.
Objective: To assess obstetric outcomes and placental findings in pregnancies attained by in vitro fertilization (IVF) in patients with diminished ovarian reserve (DOR).
Design: Retrospective cohort study.
Setting: University-affiliated tertiary hospital.
Interventions: DOR, defined as an antral follicle count (AFC) of six or less (DOR group), as compared to patients with no DOR and an antral count above six (control group).
Patients: Live singleton births after IVF between 2009 and 2017.
Main outcome measures: Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes.
Results: A total of 110 deliveries of patients with DOR were compared to 772 controls. Maternal age was higher in the DOR group, 36.3 ± 4.4 vs. 35.3 ± 4.1, p=0.02. DOR patients were more likely to have a diagnosis of endometriosis, p=0.02, and less likely a diagnosis of male factor, p<0.001, ovulation disorder, p<0.001 or tubal factor, p=0.04, or a transfer of a blastocyte, p=0.007. After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia, 8.1% vs. 2.7%, aOR 3.05 95%CI 1.33-6.97. On placental examination, DOR was associated with a higher rate of fetal vasculopathy (p=0.01) and multiple fetal vascular malperfusion lesions (p=0.03), and a lower rate of circummarginate insertion (p=0.01) and intervillous thrombosis (p=0.02).
Conclusion: DOR, specifically defined as an AFC of six or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.
An review of techniques utilised within pre-implantation genetic testing
The Outcome study examines the fate of 4083 patients beginning IVF in 41 IVF centres, between January 2010 and December 2013.
Cumulative live birth rate per patient (CLBR), the best reflection of IVF efficacy, is rarely presented in publications as it requires long-term follow-up, including all successive cycles, and pregnancies outcome.
Analysis of international publications shows an average CLBR of 41.6 % and a drop-out rate of 49.5 %, both greatly varying by country and IVF centres.
Because of the frequency with which patients change centre (8%), the Outcome study distinguishes patients with a past history of IVF in another centre (CLBR = 47.2 %) and patients undergoing their first true cycle (CLBR = 56.4 %). Survival techniques by Competing Risk, intended to take account of drop-out and lost to follow-up, assessed the overall CLBR as being 65.4 %.
Differences in performance between centres are considerable for both CLBR (32–64%) and Performance Index, taking account of the number of cycles required to achieve a pregnancy (2–5).
Multiple variance logistic regression analysis shows that the indicators influencing performance are age, parity, number of oocytes, smoking habit and overweight. These indicators are independent each other and are influencing performance in a high significant way.
After adjusting for these indicators, the differences between centres are reduced but remain large and very significant. No centre appears to have specific expertise in the management of patients with adverse indicators.
The Outcome study therefore confirms that the large differences in performance between centres are not explained by a difference in the treated population.
Polycystic ovary syndrome (PCOS) affects 6–10% of women in reproductive age. According to diagnostic criteria used, 55 to 91% of normogonadotropic anovulatory (WHO-II) women have sign and/or symptoms of the PCOS disease. Women with PCOS symptoms are more likely to be sub-fertile when compared to women without PCOS symptoms (26.5 vs. 17.1%, p < 0.001). However at the end, although time to first pregnancy increase, in women with PCOS, lifetime fertility is similar.
Research Question
The question of interest for this study is to examine the chance of a live birth following assisted reproductive technology (ART) treatment in women with epilepsy, compared to women without epilepsy. In sub-analyses the chance of biochemical and clinical pregnancies is analysed, and the impact of anti-epileptic drugs (AED) treatment prior to embryo transfer.
Design
This register-based cohort study is based on the Danish ART register comprising all women with an embryo transfer during 2006 through 2017, comprising 730 ART treatments in 264 women with a history of epilepsy, and 128,387 ART treatments in 42,938 women without epilepsy.
Adjustments were made for comorbidity, women's age, calendar year, the type of infertility treatment, and the cause of infertility. A possible impact of AED use at the time of the embryo transfer was studied in a sub-analysis. The primary outcome was live birth within a period of 140-308 days after the date of embryo transfer.
Results
The adjusted odds ratio for a live birth per embryo transfer in women with epilepsy, relative to women without epilepsy, was 1.06 (95% CI 0.88-1.28). The adjusted odds ratio for live birth among users of AED was 1.22 (95% CI 0.77-1.92), relative to women who had stopped the use of AED prior to embryo transfer.
Conclusions
The chances of a live birth per embryo transfer were similar in the women with and without epilepsy. These are novel and reassuring findings on the efficacy of infertility treatment in women with epilepsy.
Sperm DNA damage reduces pregnancy rates in couples undergoing in vitro fertilization (IVF). Because it has been shown that testicular sperm have lower DNA damage than ejaculated sperm, it is an attractive idea to consider using testicular sperm for IVF for men with high sperm DNA damage. In fact, there are multiple centers throughout the world now offering sperm retrieval for IVF to manage this condition. However, there is insufficient evidence to conclude that testicular sperm improves pregnancy/live birth rates. Further studies are required before offering sperm retrieval as a standard of care to manage high sperm DNA damage.
Objective:
To investigate the chance of live birth after several oocyte retrieval cycles in patients with diminished ovarian reserve (DOR) and identify the possible predictors.
Methods:
A retrospective analysis of 931 patients with DOR who underwent in vitro fertilization at a university hospital in China between January 2012 and December 2014. All data for fresh and the associated frozen-thawed embryo transfer attempts were analyzed. Conditional and cumulative live birth rates (LBRs) were calculated. Mediation and logistic regression analyses were performed to determine the predictors of live birth.
Results:
Conditional LBRs remained around 10.0% in the first five cycles. Conservative cumulative LBRs (CLBRs) reached 22.0% after three cycles and increased to 24.8% after six cycles; optimal CLBRs increased from 12.9% to nearly 50.0% after six cycles. Patient age and the number of good-quality embryos were two key predictors in determining the conditional and conservative LBRs.
Conclusion:
For patients with DOR, conditional LBR remained constant in the first five cycles, and patients should be encouraged to continue to three or five completed cycles to maximize their chance of live birth. Patient age and the number of good-quality embryos were two key factors to predict live birth.
The aim of this study is to evaluate the effect of severe endometriosis in younger patients compared to tubal infertility on pregnancy and live birth rate undergoing in vitro fertilization (IVF). This prospective observational study included 294 women with severe endometriosis and 358 women with tubal factor as control who underwent IVF. Follicular fluid samples were collected during oocyte retrieval, and cytokines and angiogenic factors were estimated. The groups were sub-stratified based on age. Number of metaphase II oocytes, grade I/II embryos, pregnancy rate, miscarriage rate per pregnancy, and live birth rate were compared. Significantly elevated levels of cytokines and angiogenic molecules were observed in younger endometriosis patients when compared to tubal group (p < 0.001). Number of MII oocytes (p < 0.003) and grade I/II embryos (p < 0.001) were observed to be significantly lower in these women when compared with matched controls. Despite higher levels of inflammatory cytokines, angiogenic molecules, fewer MII oocytes, and grade I/II embryos, the younger endometriosis patients had similar pregnancy (OR 0.81; 95% CI 0.54-1.22; p = 0.31) and live birth rate (OR 0.78; 95% CI 0.5-1.2; p = 0.26) when compared with matched controls. In contrast, endometriosis patients of age ≥ 35 years had significantly less likelihood of live birth (OR 0.47; 95% CI 0.25-0.9; p = 0.02) and pregnancy rate (OR 0.46; 95% CI 0.22-0.95; p = 0.03), respectively, when compared with the matched controls. It appears that women with severe endometriosis have even chance of successful pregnancy if diagnosed at early age and sought for assisted reproductive technology to reduce its adverse effect on reproductive outcome.
Research question:
Does systemic oxidative stress occur during the early follicular phase of the menstrual cycle in infertile women with minimal (stage I) or mild (stage II) endometriosis? Are serum oxidative stress markers during the early follicular phase of the menstrual cycle good predictors of successful gestation in these women who undergo ovarian stimulation for intracytoplasmic sperm injection (ICSI)?
Materials and methods:
A pilot study (prospective case-control study) was conducted in a University Hospital. Serum samples were obtained during the early follicular phase of the natural cycle preceding ovarian stimulation for ICSI of infertile women (with and without stage I and II endometriosis, the latter having male factor infertility). Total hydroperoxides (FOX1), malondialdehyde, advanced oxidation protein products, reduced glutathione, superoxide dismutase, total antioxidant capacity (TAC), 8-hydroxy-2'-deoxyguanosine (8OHdG) and vitamin E were analysed in serum from 35 women with stage I or II endometriosis and 60 control women. The accuracy of oxidative stress markers for predicting clinical pregnancy and live births was determined by receiver operator characteristic curves.
Results:
Women with stage I and II endometriosis showed lower serum 8OHdG concentrations (16.02 ng/ml) compared with the control group (22.08 ng/ml). The best predictor for clinical pregnancy and live births was TAC, whereas FOX1 was the best predictor of clinical pregnancy in the control group.
Conclusions:
Infertile women with stage I and II endometriosis present systemic oxidative stress during the early follicular phase of the menstrual cycle. Some oxidative stress markers were good predictors of clinical pregnancy and live births after ICSI. Serum TAC was predictive of clinical pregnancy and live births after ICSI in women with stage I or II endometriosis.
Background:
Assisted reproductive techniques (ART) have been extensively used to treat infertility. Inaccurate prediction of a couple's fertility often leads to lowered self-esteem for patients seeking ART treatment and causes fertility distress.
Objective:
This prospective study aimed to statistically analyze patient data from a single reproductive medical center over a period of 18 months, and to establish mathematical models that might facilitate accurate prediction of successful pregnancy when ART are used.
Methods:
In the present study, we analyzed clinical data prospectively collected from 760 infertile patients visiting the second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between June 1, 2016 and December 31, 2017. Various advanced statistical methods, including broken-line regression, were employed to analyze the data.
Results:
Age remained the most important factor affecting the outcome of IVF/ICSI. Using broken-line regression model, the fastest clinical pregancy declining age was between 25 and 32. Female infertility type was found to be a key predictor for the numer of good-quality embryos and successful pregnancy, along with the antral follicle count (AFC), total number of embryos, recombinant follicle stimulating hormones (rFSH) dosage, estradiol (E2) on the trigger day, and total number of oocytes retrieved. rFSH dosage was also significantly associated with the number of oocytes retrieved and the number of frozen embryos.
Conclusion:
The fastest clinical pregancy declining age is ranged between 25 and 32, and female infertility type is evidenced as another key predictive factor for the cumulative outcome of ART.
Objectives
No studies have examined the efficacy of assisted reproductive technology (ART) treatment in women with rheumatoid arthritis. Therefore, we examined the chance of live birth after ART treatment in women with rheumatoid arthritis compared with women without rheumatoid arthritis.
Methods
Our cohort study is based on nationwide Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 30 June 2017. The cohorts comprised 1149 embryo transfers in women with rheumatoid arthritis, and 198 941 embryo transfers in women without rheumatoid arthritis. Our outcome was live birth per embryo transfer, and we controlled for multiple covariates in the analyses. In subanalyses, we examined a chance of biochemical/clinical pregnancy after ART and a possible impact of corticosteroid use prior to embryo transfer.
Results
The adjusted OR (aOR) for a live birth per embryo transfer in women with rheumatoid arthritis, relative to women without rheumatoid arthritis, was 0.78 (95% CI 0.65 to 0.92). The aORs for biochemical and clinical pregnancies were 0.81 (95% CI 0.68 to 0.95) and 0.82 (95% CI 0.59 to 1.15), respectively. Corticosteroid prescription prior to embryo transfer increased the OR for live birth (aOR=1.32 (95% CI 0.85 to 2.05)).
Conclusions
The chance of a live birth was significantly reduced in women with rheumatoid arthritis receiving ART treatment, relative to women without rheumatoid arthritis, and our result suggested that the problem was related to an impaired chance of embryo implantation. The role of corticosteroid use prior to embryo transfer must be a subject for further research.
OBJECTIVE: To compare the predictive accuracy of a formula combining age, anti-Müllerian hormone (AMH), antral follicle count (AFC), and follicle-stimulating hormone (FSH) with those individual markers in predicting poor ovarian response (POR) in young, nonobese women undergoing their first IVF cycle. STUDY DESIGN: Women aged <40 y, FSH <10 IU/L, BMI <30 kg/m²undergoing first IVF cycle. POR was defined as ≤3 oocytes retrieved or cycle cancellation. The predictive accuracy of each marker alone and the formula combining the 4 markers were determined by area under the receiver operating characteristic curve (AU-ROC). Additionally, we examined the cutoff values and false-positive rates (FPRs) for predicting POR at detection rates of 50% and 80%. RESULTS: Of the 141 women we evaluated, 45 had POR. The AU-ROC of the combined parameters (0.82) was significantly higher than that for the individual parameters: age=0.67, AFC=0.74, AMH=0.75, and FSH=0.61. For a detection rate of 50%, the formula had FPR=10%, while the individual markers had FPR= 13–24%; for a detection rate of 80%, the formula had FPR=27%, while the individual markers had FPR= 42–72%. CONCLUSION: Combining age, AMH, AFC, and FSH is significantly more accurate than those individual markers for the prediction of POR.
This paper analyses the efficacy data from assisted reproduction clinics, obtained from both scientific society reports and from studies published in specialised journals, in order to compare them with information published by Spanish assisted reproduction clinics on their websites. It aims to verify whether this information matches the reality of the findings in the media analysed or, in contrast, differs from the aforementioned scientific evidence. Our study shows marked discrepancies between the evidence of existing statistical data, and figures published by most of the clinics on their websites, which could constitute false advertising.
Background:
It is unknown whether the risk of adverse outcomes in twin pregnancies among subfertile women, conceived with and without in vitro fertilization, differs from those conceived spontaneously.
Objective:
We sought to evaluate the effects of fertility status on adverse perinatal outcomes in twin pregnancies on a population basis.
Study design:
All twin live births of ≥22 weeks' gestation and ≥350 g birthweight to Massachusetts resident women in 2004 through 2010 were linked to hospital discharge records, vital records, and in vitro fertilization cycles. Women were categorized by their fertility status as in vitro fertilization, subfertile, or fertile, and by twin pair genders (all, like, unlike). Women whose births linked to in vitro fertilization cycles were classified as in vitro fertilization; those with indicators of subfertility but without in vitro fertilization treatment were classified as subfertile; all others were classified as fertile. Risks of 6 adverse pregnancy outcomes (gestational diabetes, pregnancy hypertension, uterine bleeding, placental complications [placenta abruptio, placenta previa, and vasa previa], prenatal hospitalizations, and primary cesarean) and 9 adverse infant outcomes (very low birthweight, low birthweight, small-for-gestation birthweight, large-for-gestation birthweight, very preterm [<32 weeks], preterm, birth defects, neonatal death, and infant death) were modeled by fertility status with the fertile group as reference, using multivariate log binomial regression and reported as adjusted relative risk ratios and 95% confidence intervals.
Results:
The study population included 10,352 women with twin pregnancies (6090 fertile, 724 subfertile, and 3538 in vitro fertilization). Among all twins, the risks for all 6 adverse pregnancy outcomes were significantly increased for the subfertile and in vitro fertilization groups, with highest risks for uterine bleeding (adjusted relative risk ratios, 1.92 and 2.58, respectively) and placental complications (adjusted relative risk ratios, 2.07 and 1.83, respectively). Among all twins, the risks for those born to subfertile women were significantly increased for very preterm birth and neonatal and infant death (adjusted relative risk ratios, 1.36, 1.89, and 1.87, respectively). Risks were significantly increased among in vitro fertilization twins for very preterm birth, preterm birth, and birth defects (adjusted relative risk ratios, 1.28, 1.07, and 1.26, respectively).
Conclusion:
Risks of all maternal and most infant adverse outcomes were increased for subfertile and in vitro fertilization twins. Among all twins, the highest risks were for uterine bleeding and placental complications for the subfertile and in vitro fertilization groups, and neonatal and infant death in the subfertile group. These findings provide further evidence supporting single embryo transfer and more cautious use of ovulation induction.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effectiveness and safety of intentional endometrial injury performed in women or couples attempting to conceive through sexual intercourse or intrauterine insemination.
Background:
Births to subfertile women, with and without infertility treatment, have been reported to have lower birthweights and shorter gestations, even when limited to singletons. It is unknown whether these decrements are due to parental characteristics or aspects of infertility treatment.
Objective:
To evaluate the effect of maternal fertility status on the risk of pregnancy, birth, and infant complications STUDY DESIGN: All singleton live births of ≥22 weeks' gestation and ≥350 grams birthweight to Massachusetts resident women in 2004-10 were linked to hospital discharge and vital records. Women were categorized by their fertility status as in vitro fertilization (IVF), subfertile, or fertile. Women whose births linked to IVF cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System were classified as IVF. Women with indicators of subfertility but not treated with IVF were classified as subfertile. Women without indicators of subfertility or IVF treatment were classified as fertile. Risks of fifteen adverse outcomes (gestational diabetes, pregnancy hypertension, antenatal bleeding, placental complications (placenta abruptio and placenta previa), prenatal hospitalizations, primary cesarean, very low birthweight (<1,500g), low birthweight (<2,500g), small-for-gestation birthweight (Z-score ≤-1.28), large-for-gestation birthweight (Z-score ≥1.28), very preterm (<32 weeks), preterm (<37 weeks), birth defects, neonatal death (0-27 days), and infant death (0-364 days of life) were modeled by fertility status with the fertile group as reference, and the subfertile group as reference, using multivariate log binomial regression and reported as adjusted risk ratios (ARRs) and 95% confidence intervals.
Results:
The study population included 459,623 women (441,420 fertile, 8,054 subfertile, and 10,149 IVF). Women in the subfertile and IVF groups were older than their fertile counterparts. Risks for six out of six pregnancy outcomes and six out of nine infant outcomes were increased for the subfertile group, and five out of six pregnancy outcomes and seven out of nine infant outcomes were increased for the IVF group. For four of the six pregnancy outcomes (uterine bleeding, placental complications, prenatal hospitalizations, and primary cesarean) and two of the infant outcomes (low birthweight and preterm) the risk was greater in the IVF group, with non-overlapping confidence intervals to the subfertile group, indicating a substantially higher risk among IVF-treated women. The highest risks for the IVF women were uterine bleeding (ARR 3.80, 95% CI 3.31, 4.36) and placental complications (ARR 2.81, 95% CI 2.57, 3.08), and for IVF infants, very preterm birth (ARR 2.13, 95% CI 1.80, 2.52) and very low birthweight (ARR 2.15, 95% CI 1.80, 2.56). With subfertile women as reference, risks for the IVF group were significantly increased for uterine bleeding, placental complications, prenatal hospitalizations, primary cesarean, low and very low birthweight, and preterm and very preterm birth.
Conclusions:
These analyses indicate that, compared to fertile women, subfertile and IVF-treated women tend to be older, have more pre-existing chronic conditions, and are at higher risk for adverse pregnancy outcomes, particularly uterine bleeding and placental complications. The greater risk in IVF-treated women may reflect more severe infertility, more extensive underlying pathology, or other unfavorable factors not measured in this study.
Background:
In this study, we analyze the chance of a live birth and the impact of inflammatory bowel disease surgery in women with Crohn's disease (CD) or ulcerative colitis (UC) who have undergone assisted reproductive technology (ART) treatments.
Methods:
This is a nationwide cohort study based on the Danish health registries. We compare all women with and without CD or UC who received a first time ART treatment from January 1, 1994 to June 30, 2012 with follow-up until December 31, 2013. Our outcome was live birth per woman within 18 months after the first ART treatment. We adjusted for multiple covariates and looked specifically at CD and UC surgeries before ART.
Results:
In all, 381 women with UC, 158 women with CD, and 50,321 women without inflammatory bowel disease received first time ART treatments. In women with UC, the adjusted odds ratio (OR) of a live birth was 0.82 (95% confidence interval [CI], 0.57-1.17). In women with CD, the adjusted OR of a live birth was 0.58 (95% CI, 0.32-1.03). In women with CD having previous CD surgery versus no CD surgery, the adjusted OR of a live birth was significantly decreased (0.29, 95% CI, 0.13-0.65). In women with UC with previous UC surgery, the similar OR was 0.81 (95% CI, 0.47-1.40).
Conclusions:
In women with CD surgery, the chance of a live birth within 18 months after initiation of ART treatment was significantly decreased. This knowledge should help patients make decisions regarding pregnancy planning.
Background:
Intentional endometrial injury is currently being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy or a similar technique, and is a common, simple, gynaecological procedure that has an established safety profile. However, it is also known to be associated with a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with low complexity fertility treatments such as intrauterine insemination (IUI) and ovulation induction (OI), remains unclear.
Objectives:
To evaluate the effectiveness and safety of intentional endometrial injury in subfertile women and couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI).
Search methods:
We searched the Cochrane Gyanecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, DARE, ISI Web of Knowledge and ClinicalTrials.gov; as well as reference lists of relevant reviews and included studies. We performed the searches from inception to 31 October 2015.
Selection criteria:
We included randomised controlled trials (RCTs) that evaluated any kind of intentional endometrial injury in women planning to undergo IUI or attempting to conceive spontaneously (with or without OI) compared to no intervention, a mock intervention or intentional endometrial injury performed at a different time or to a higher/lower degree.
Data collection and analysis:
Two review authors independently selected trials, extracted data and assessed trial quality using GRADE methodology. The primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Secondary outcomes were clinical pregnancy, miscarriage, ectopic pregnancy, multiple pregnancy and bleeding secondary to the procedure. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I(2) statistic.
Main results:
Nine trials, which included a total of 1512 women, met the inclusion criteria of this Cochrane review. Most of these studies included women with unexplained infertility. In seven studies the women were undergoing IUI and in two studies the women were trying to conceive from sexual intercourse. Eight trials compared intentional endometrial injury with no injury/placebo procedure; of these two trials also compared intentional endometrial injury in the cycle prior to IUI with intentional endometrial injury in the IUI cycle. One trial compared higher vs. lower degree of intentional endometrial injury. Intentional endometrial injury vs. either no intervention or a sham procedureWe are uncertain whether endometrial injury improves live birth/ongoing pregnancy as the quality of the evidence has been assessed as very low (risk ratio (RR) 2.22, 95% confidence interval (CI) 1.56 to 3.15; six RCTs, 950 participants; I² statistic = 0%, very low quality evidence). When we restricted the analysis to only studies at low risk of bias the effect was imprecise and the evidence remained of very low quality (RR 2.64, 95% CI 1.03 to 6.82; one RCT, 105 participants; very low quality evidence). Endometrial injury may improve clinical pregnancy rates however the evidence is of low quality (RR 1.98, 95% CI 1.51 to 2.58; eight RCTs, 1180 participants; I² statistic = 0%, low quality evidence).The average pain experienced by participants undergoing endometrial injury was 6/10 on a zero-10 visual analogue scale (VAS)(standard deviation = 1.5). However, only one study reported this outcome. Higher vs. lower degree of intentional endometrial injuryWhen we compared hysteroscopy with endometrial injury to hysteroscopy alone, there was no evidence of a difference in ongoing pregnancy rate (RR 1.29, 95% CI 0.71 to 2.35; one RCT, 332 participants; low quality evidence) or clinical pregnancy rate (RR 1.15, 95% CI 0.66 to 2.01; one RCT, 332 participants, low quality evidence). This study did not report the primary outcome of pain during the procedure. Timing of intentional endometrial injuryWhen endometrial injury was performed in the cycle prior to IUI compared to the same cycle as the IUI, there was no evidence of a difference in ongoing pregnancy rate (RR 0.65, 95% CI 0.37 to 1.16, one RCT, 176 participants; very low quality evidence) or clinical pregnancy rate (RR 0.82, 95% CI 0.50 to 1.36; two RCTs, 276 participants; very low quality evidence). Neither of these studies reported the primary outcome of pain during the procedure.In all three comparisons there was no evidence of an effect on miscarriage, ectopic pregnancy or multiple pregnancy. No studies reported bleeding secondary to the procedure.
Authors' conclusions:
It is uncertain whether endometrial injury improves the probability of pregnancy and live birth/ongoing pregnancy in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution as we graded the quality of the evidence as either low or very low. The main reasons we downgraded the quality of the evidence were most included studies were at a high risk of bias and had an overall low level of precision. Further well-conducted RCTs that recruit large numbers of participants and minimise internal bias are required to confirm or refute these findings.
Objectives
The objective of this study is to examine whether the endometrial thickness and the presence of endometrioma are independent predictors of clinical pregnancy rate, or just associated with a poor ovarian response (POR).Methods
This is a retrospective cohort study assessing the first cycle of all women undergoing IVF/ICSI in a university hospital in Brazil in the period between January 2011 and December 2012. Only the first cycle of each woman within the period was considered; women aged > 40 years, women who used clomiphene citrate during COS, and women who did not undergo embryo transfer were excluded from analysis. POR was defined as ≤3 oocytes retrieved, and a thin endometrium was defined as an endometrial thickness ≤ 7.0 mm on the day of hCG. We performed a multiple regression analysis to identify which of the following parameters were independent predictors of clinical pregnancy: age, number of oocytes retrieved, endometrial thickness, and the presence of endometrioma.ResultsWithin the study period, 787 women started controlled ovarian stimulation, but 270 were excluded from analysis. Within the 517 analyzed women, those who become pregnant were younger and yielded more oocytes. The proportion of POR was higher in women with a thin endometrium (17/57 = 30% vs. 80/460 = 17%, p = 0.03) and in women with endometrioma (15/39 = 38.5% vs. 82/478, p = 0.002). The results of our regression analysis showed that only the woman's age and the number of oocytes retrieved were independent predictors of pregnancy. Additionally, we observed that clinical pregnancy rates were good in women with thin endometrium who retrieved at least ≥ 7 oocytes (11/25 = 44% vs. 99/241 = 41%, thin vs. normal endometrium) and in women with endometrioma who retrieved at least 4 oocytes (9/24 = 38% vs. 158/396 = 40%, women with vs. without endometrioma).Conclusion
Both a thin endometrial thickness and the presence of endometrioma are related with POR, but they are not important independent predictors of clinical pregnancy. Good pregnancy rates are observed when these conditions are observed in women with a good ovarian response.
OBJECTIVE: To evaluate assisted reproductive technology (ART) pregnancy outcomes by infertility diagnosis. STUDY DESIGN: ART data on women who were treated and gave birth in Massachusetts were linked to vital records and hospital utilization data. Live births were categorized by 8 mutually exclusive ART diagnoses. Risks of prematurity, low birthweight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA), pregnancy hypertension, gestational diabetes, prenatal hospitalizations, and primary cesarean delivery were modeled using logistic regression, adjusted for parental characteristics, treatment parameters, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals); the reference group were pregnancies with the diagnosis of male factor. RESULTS: Among the 7,354 singleton and twin pregnancies, there were nonsignificant differences in the risks for LBW, SGA, or LGA. Significantly increased risks included gestational diabetes (ovulation disorders, AOR 1.80, 1.35–2.41), prematurity (ovulation disorders, AOR 1.36, 1.08–1.71; other factors, AOR 1.33, 1.05–1.67), prenatal hospital admissions (endometriosis, tubal and other factors, ovulation disorders, and uterine factors, AORs ranging from 1.66– 2.68), and primary cesarean section (uterine factors, AOR 1.96, 1.15–3.36). CONCLUSION: Although the infant outcomes of LBW, SGA, and LGA were generally similar across diagnosis groups, specific diagnoses had greater risks for prematurity, gestational diabetes, prenatal hospital utilization, and primary cesarean delivery.
Endometriosis is a common gynecologic disorder that persists throughout the reproductive years. Although endometriosis is a surgical diagnosis, medical management with ovarian suppression remains the mainstay of long-term management with superimposed surgical intervention when needed. The goal of surgery should be excision or ablation of all visible disease to minimize risk of recurrence and need for repeat surgeries. When infertility is the presenting symptom, surgical therapy in addition to assisted reproductive technology can improve chances of conception; however, the treatment approach depends on stage of disease and other patient characteristics that affect fecundity.
Copyright © 2015 Elsevier Inc. All rights reserved.
Objective
Evaluate whether the presence or severity of endometriosis affect the outcomes of assisted reproductive techniques (ART).Methods
In this systematic review all studies comparing the ART outcomes of women with and without endometriosis or at different stages of the disease were considered eligible. We used either risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) for comparisons. Our primary outcome was live birth; the secondary outcome was clinical pregnancy. Miscarriage and the number of oocytes retrieved were examined as additional outcomes.ResultsWe included 90 studies in the review and 76 in the meta-analysis: 20,167 women with endometriosis were compared with 121,931 women without endometriosis; and 1,703 women with endometriosis III/IV were compared with 2,227 women with endometriosis I/II. The following results were observed for the comparison women with endometriosis vs. women without endometriosis: live birth, RR=0.99 (95%IC=0.92-1.06); clinical pregnancy, RR=0.95 (95%IC=0.89-1.02); miscarriage, RR=1.31 (95%IC=1.07-1.59); number of oocytes retrieved, MD= − 1.56 (95%IC= − 2.05 to −1.08). The following results were observed for the comparison women with endometriosis III/IV vs. I/II: live birth, RR=0.94 (95%CI=0.80-1.11); clinical pregnancy, RR=0.90 (95%CI=0.82-1.00); miscarriage, RR=0.99 (95%CI=0.73-1.36); number of oocytes retrieved, MD= − 1.03 (95%CI= − 1.67 to −0.39).Conclusions
Women with endometriosis undergoing ART have practically the same chance of achieving clinical pregnancy and live birth than women with other causes of infertility. No relevant difference was observed in the chance of achieving clinical pregnancy and live birth following ART when comparing endometriosis III/IV with endometriosis I/II. The quality of the evidence for the additional examined outcomes was very low, not allowing meaningful conclusions.
Objectives:
This report presents 2011 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal characteristics, including age, live-birth order, race and Hispanic origin, marital status, attendant at birth, method of delivery, and infant characteristics (e.g., period of gestation, birthweight, and plurality). Birth and fertility rates are presented by age, live-birth order, race and Hispanic origin, and marital status. Selected data by mother's state of residence and birth rates by age and race of father also are shown. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.
Methods:
Descriptive tabulations of data reported on the birth certificates of the 3.95 million births that occurred in 2011 are presented. Denominators for population-based rates are postcensal estimates derived from the U.S. 2010 census. Birth and fertility rates for 2001-2009 are based on revised intercensal population estimates. Denominators for 2011 and 2010 rates for the specific Hispanic groups are derived from the American Community Survey; denominators for earlier years are derived from the Current Population Survey.
Results:
The number of births declined 1% in 2011 to 3,953,590. The general fertility rate also declined 1%, to 63.2 per 1,000 women aged 15-44. The teen birth rate fell 8%, to 31.3 per 1,000 women. Birth rates declined for women in their 20s, were unchanged for women aged 30-34, and rose for women aged 35-44. The total fertility rate (estimated number of births over a woman's lifetime) declined 2% to 1,894 per 1,000 women. The number and rate of births to unmarried women declined; the percentage of births to unmarried women was essentially stable at 40.7%. The cesarean delivery rate was unchanged from 2010 at 32.8%. The preterm birth rate declined for the fifth straight year to 11.73%; the low birthweight rate declined slightly to 8.10%. The twin birth rate was not significantly changed at 33.2 per 1,000 births; the rate of triplet and higher-order multiple births also was essentially stable at 137.0 per 100,000.
Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure.
We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment.
The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.
Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).
This report presents 2009 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal characteristics including age, live-birth order, race and Hispanic origin, marital status, hypertension during pregnancy, attendant at birth, method of delivery, and infant characteristics (period of gestation, birthweight, and plurality). Birth and fertility rates by age, live-birth order, race and Hispanic origin, and marital status also are presented. Selected data by mother's state of residence are shown, as well as birth rates by age and race of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.
Descriptive tabulations of data reported on the birth certificates of the 4.13 million births that occurred in 2009 are presented. Denominators for population-based rates are postcensal estimates derived from the U.S. 2000 census.
The number of births declined to 4,130,665 in 2009, 3 percent less than in 2008. The general fertility rate declined 3 percent to 66.7 per 1,000 women aged 15-44 years. The teenage birth rate fell 6 percent to 39.1 per 1,000. Birth rates for women in each 5-year age group from 20 through 39 years declined, but the rate for women 40-44 years continued to rise. The total fertility rate (estimated number of births over a woman's lifetime) was down 4 percent to 2,007.0 per 1,000 women. The number and rate of births to unmarried women declined, whereas the percentage of nonmarital births increased slightly to 41.0. The cesarean delivery rate rose again, to 32.9 percent. The preterm birth rate declined to 12.18 percent; the low birthweight rate was stable at 8.16 percent. The twin birth rate increased to 33.2 per 1,000; the triplet and higher-order multiple birth rate rose 4 percent to 153.5 per 100,000.
The current trends to postpone motherhood and the increase in demand for assistance in reproductive medicine highlight the need for seeking guidelines for the establishment of individualized treatment protocols. Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, but they may occupy important place in initial counseling, predicting unsatisfactory results that could be improved by individualized induction schemes and reducing excessive psychological and financial burdens, and adverse effects. In this paper, we revise the role of hormonal basal and dynamic tests, as well as ultrasonographic markers, as ovarian reserve markers, in order to provide embasement for propaedeutic strategies and their interpretation in order to have reproductive success.
The higher prevalence of preterm birth (PTB) and low birthweight (LBW) following infertility treatment may relate to the treatment itself or indicate that subfertility predisposes to a higher risk. Our aim was to examine whether basal FSH levels are related to the risk for PTB and LBW among pregnancies resulting from IVF.
We studied a retrospective cohort in the 2008 National Society for Assisted Reproductive Technology Database, including all women who underwent a fresh non-donor IVF cycle resulting in a singleton live birth having a recorded basal serum FSH value (n = 14 262). The FSH value used was either the maximum basal or clomiphene-stimulated serum level. Log binomial models were created to assess the associations between FSH and PTB (<37 weeks), and between FSH and LBW (<2500 g), adjusting for maternal age, ethnicity, gravidity/parity, history of PTB, smoking, BMI and infant gender.
Data for 14 086 patients were analyzed. FSH levels were inversely related to the risk of PTB and LBW. Women in the highest quartile of FSH levels (≥ 9 mIU/ml) had the longest adjusted mean gestational age (271.2 days), the lowest adjusted relative risk (RR) of PTB [0.87, 95% confidence interval (CI): 0.76-1.01], the highest adjusted mean birthweight (3249 g) and the lowest adjusted RR of LBW (0.89, 95% CI: 0.73-1.04).
The inverse relationship between maximal basal FSH levels and the risk for PTB and LBW in singleton IVF gestations suggests that diminished ovarian reserve is not the primary mediator of the increased prevalence of PTB and LBW in IVF pregnancies.
Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Although patients with PCOS are typically characterized by increased numbers of oocytes retrieved during IVF, they are often of poor quality, leading to lower fertilization, cleavage and implantation rates, and a higher miscarriage rate.
For this review, we searched the database MEDLINE (1950 to January 2010) and Google for all full texts and/or abstract articles published in English with content related to oocyte maturation and embryo developmental competence.
The search showed that alteration of many factors may directly or indirectly impair the competence of maturating oocytes through endocrine and local paracrine/autocrine actions, resulting in a lower pregnancy rate in patients with PCOS. The extra-ovarian factors identified included gonadotrophins, hyperandrogenemia and hyperinsulinemia, although intra-ovarian factors included members of the epidermal, fibroblast, insulin-like and neurotrophin families of growth factors, as well as the cytokines.
Any abnormality in the extra- and/or intra-ovarian factors may negatively affect the granulosa cell-oocyte interaction, oocyte maturation and potential embryonic developmental competence, contributing to unsuccessful outcomes for patients with PCOS who are undergoing assisted reproduction.
The increased risk of low birth weight associated with the use of assisted reproductive technology has been attributed largely to the higher rate of multiple gestations associated with such technology. It is uncertain, however, whether singleton infants conceived with the use of assisted reproductive technology may also have a higher risk of low birth weight than those who are conceived spontaneously.
We used population-based data to compare the rates of low birth weight (less-than-or-equal 2500 g) and very low birth weight (<1500 g) among infants conceived with assisted reproductive technology with the rates in the general population.
We studied 42,463 infants who were born in 1996 and 1997 and conceived with assisted reproductive technology and used as a comparison group 3,389,098 infants born in the United States in 1997. Among singleton infants born at 37 weeks of gestation or later, those conceived with assisted reproductive technology had a risk of low birth weight that was 2.6 times that in the general population (95 percent confidence interval, 2.4 to 2.7). The use of assisted reproductive technology was associated with an increased rate of multiple gestations; however, its use was not associated with a further increase in the risk of low birth weight in multiple births. Among twins, the ratio of the rate of low birth weight after the use of assisted reproductive technology to the rate in the general population was 1.0 (95 percent confidence interval, 1.0 to 1.1). Infants conceived with assisted reproductive technology accounted for 0.6 percent of all infants born to mothers who were 20 years of age or older in 1997, but for 3.5 percent of low-birth-weight and 4.3 percent of very-low-birth-weight infants.
The use of assisted reproductive technology accounts for a disproportionate number of low-birth-weight and very-low-birth-weight infants in the United States, in part because of absolute increases in multiple gestations and in part because of higher rates of low birth weight among singleton infants conceived with this technology.
Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.
Conventionally, most in vitro fertilization (IVF) embryos are transferred in fresh treatment cycles with freezing reserved for spare ones. Improvement
in cryopreservation facilities over time has encouraged the greater use of this technology with the success rate of frozen
replacement cycles approaching that associated with fresh embryo transfer. Data from observational studies suggest that obstetric
and perinatal outcomes are better in pregnancies resulting from frozen replacement cycles. In the interests of promoting feto-maternal
safety is it therefore time to avoid fresh embryo transfers in IVF, freeze all available embryos and replace them in subsequent
cycles? In this article we explore the biological plausibility of this concept, appraise the evidence underpinning it and
consider the implications of adopting such a strategy in routine clinical practice. The outcomes of existing randomized trials
appear to favour a strategy of frozen embryo transfer, but larger trials are needed before a major change in clinical practice
can be considered.
Singleton neonates born after in vitro fertilization (IVF) are at increased risk for low birth weight, preterm delivery, or both. We sought to assess whether the alteration of the peri-implantation maternal environment resulting from ovarian stimulation may contribute to increased risk of low birth weight in IVF births.
The Society for Assisted Reproductive Technologies database was used to identify IVF-conceived neonates born in the United States between 2004 and 2006. Associations were assessed in neonates born after fresh compared with frozen and thawed embryo transfer in women of similar ovarian responsiveness, in paired analysis of neonates born to the same woman after both types of embryo transfer, and in neonates born after oocyte donation.
Of 56,792 neonates identified, 38,626 and 18,166 were conceived after transfer of fresh and frozen embryos, respectively. In singletons, there was no difference in preterm delivery. However, the odds of overall low birth weight (10% compared with 7.2%; adjusted odds ratio [OR] 1.35; 95% confidence interval [CI] 1.20-1.51), low birth weight at term (2.5% compared with 1.2%, adjusted OR 1.73, 95% CI 1.31-2.29), and preterm low birth weight (34.1% compared with 23.8%, adjusted OR 1.49, 95% CI 1.24-1.78) were all significantly higher after fresh embryo transfer. In singletons, after either fresh or frozen embryo transfer in the same patient, this association was even stronger (low birth weight: 11.5% compared with 5.6%, adjusted OR 4.66, 95% CI 1.18-18.38). In oocyte donor recipients who do not undergo any ovarian hormonal stimulation for either a fresh or a frozen embryo transfer, no difference in low birth weight was demonstrated (11.5% compared with 11.3% adjusted OR 0.99, 95% CI 0.82-1.18).
The ovarian stimulation-induced maternal environment appears to represent an independent mediator contributing to the risk of low birth weight, but not preterm delivery, in neonates conceived after IVF.
II.
To evaluate the outcomes of assisted reproductive technology (ART) cycles for male factor infertility, and method of sperm collection.
Historic cohort study.
Clinic-based data.
Cycles from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database for 2004 to 2008 were limited to three groups: non-intracytoplasmic sperm injection (ICSI) and ICSI cycles for tubal ligation only; non-ICSI and ICSI cycles for male factor infertility only; and all cycles (regardless of infertility diagnosis) using ICSI only. INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): Multivariate logistic regression was used to model the adjusted odds ratio (AOR) of clinical intrauterine gestation (CIG) and live birth (LB) rates for tubal ligation versus male factor infertility only; ICSI versus non-ICSI for male factor infertility only; and ICSI outcomes based on method of sperm collection.
Models for male factor infertility only versus tubal ligation only ICSI cycles had lower CIG (AOR 0.92) but not LB (AOR 0.87). No difference was seen for non-ICSI cycles. Within male factor infertility only cycles, ICSI had a worse outcome than non-ICSI for CIG (AOR 0.93) but not for LB (AOR 0.94). For all ICSI cycles with no male factor infertility and ejaculated sperm as the reference group, models showed better rates of CIG with male factor infertility ejaculated sperm (AOR 1.07) and with male factor infertility aspirated sperm (AOR 1.09). The LB rate was higher with male factor infertility ejaculated sperm only (AOR 1.04).
The ICSI and sperm source influence CIG and LB rates in male factor infertility cases.
The National Institute of Child Health and Human Development held a workshop on September 12-13, 2005, to summarize the risks for adverse pregnancy outcomes after assisted reproductive technology (ART), develop an approach to counseling couples regarding these risks, and establish a research agenda. Although the majority of ART children are normal, there are concerns about the increased risk for adverse pregnancy outcomes. More than 30% of ART pregnancies are twins or higher-order multiple gestations (triplets or greater) and more than one half of all ART neonates are the products of multifetal gestations, with an attendant increase in prematurity complications. Assisted reproductive technology singleton pregnancies also demonstrate increased rates of perinatal complications-small for gestational age infants, preterm delivery, and perinatal mortality-as well as maternal complications, such as preeclampsia, gestational diabetes, placenta previa, placental abruption, and cesarean delivery. Although it is not possible to separate ART-related risks from those secondary to the underlying reproductive pathology, the overall increased frequency of obstetric complications, including preterm birth and small for gestational age neonates, should be discussed with the couple. Significant gaps in knowledge were identified, and the basic science and clinical and epidemiologic research required to address these gaps is outlined.
To determine whether the first cycle of assisted reproductive technology (ART) predicts treatment course and outcome.
Retrospective study of linked cycles.
Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.
A total of 6,352 ART patients residing or treated in Massachusetts with first treatment cycle in 2004-2005 using fresh, autologous oocytes and no prior ART. Women were categorized by first cycle as follows: Group I, no retrieval; Group II, retrieval, no transfer; Group III, transfer, no embryo cryopreservation; Group IV, transfer plus cryopreservation; and Group V, all embryos cryopreserved.
None.
Cumulative live-birth delivery per woman, use of donor eggs, intracytoplasmic sperm injection (ICSI), or frozen embryo transfers (FET).
Groups differed in age, baseline FSH level, prior gravidity, diagnosis, and failure to return for Cycle 2. Live-birth delivery per woman for groups I through V for women with no delivery in Cycle I were 32.1%, 35.9%, 40.1%, 53.4%, and 51.3%, respectively. Groups I and II were more likely to subsequently use donor eggs (14.5% and 10.9%). Group II had the highest use of ICSI (73.3%); Group III had the lowest use of FET (8.9%).
Course of treatment in the first ART cycle is related to different cumulative live-birth delivery rates and eventual use of donor egg, ICSI, and FET.
To determine the feasibility of linking assisted reproductive technology (ART) cycles for individual women to compare per-cycle and cumulative live-birth rates.
Historical cohort study.
Clinic-based data.
A total of 27,906 ART cycles with residency or treatment in Massachusetts during 2004-2006 and reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) on-line database.
None.
Per-cycle and cumulative live-birth rates.
Linkage of cycles up to and including the first live-birth delivery revealed 14,265 women who averaged 1.9+/-1.2 SD cycles (range 1-11). These cycles yielded 9,452 pregnancies resulting in 7,675 live-birth deliveries. From cycle 1 to cycle 4, the cumulative live-birth rate for all patients increased from 30.4% to 43.3%, 49.1%, and 51.9%, respectively, and plateaued thereafter at about 53%. The cumulative live-birth rate after three cycles using donor oocytes was approximately 60% for women aged<43 years and >50% for women>or=43 years; for autologous oocytes it was 60.1% for ages<35 years and declined steadily to 8.5% for ages>or=43 years.
The results demonstrate the feasibility of linking ART cycles for individual women from SART CORS to characterize cumulative live-birth rates.
Over the past decade, significant advances have occurred in the diagnosis and treatment of reproductive disorders. In this review, we discuss the routine testing performed to diagnose unexplained infertility. We also discuss additional testing, such as assessment of ovarian reserve, and the potential role of laparoscopy in the complete workup of unexplained infertility. Finally, we outline the available therapeutic options and discuss the efficacy and the cost-effectiveness of the existing treatment modalities. The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile, and cost considerations.
This report presents preliminary data for 2000 on births in the United States. U.S. data on births are shown by age, race, and Hispanic origin of mother. Data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented.
Data in this report are based on more than 96 percent of births for 2000. The records are weighted to independent control counts of births received in State vital statistics offices in 2000. Comparisons are made with 1999 final data.
The number of births rose 3 percent between 1999 and 2000. The crude birth rate increased to 14.8 per 1,000 population in 2000, 2 percent higher than the 1999 rate. The fertility rate rose 3 percent to 67.6 per 1,000 women aged 15-44 years between 1999 and 2000. The birth rate for teenagers, which has been falling since 1991, declined 2 percent in 2000 to 48.7 births per 1,000 females aged 15-19 years, another historic low. The rate for teenagers 15-17 years fell 4 percent, and the rate for 18-19 year olds was down 1 percent. Since 1991, rates have fallen 29 percent for teenagers 15-17 years and 16 percent for teenagers 18-19 years. Birth rates for all of the older age groups increased for 1999-2000: 1 percent among women aged 20-24 years, 3 percent for women aged 25-29 years, and 5 percent for women in their thirties. Rates for women aged 40-54 years were also up for 2000. The birth rate for unmarried women increased 2 percent to 45.2 births per 1,000 unmarried women aged 15-44 years in 2000, but was still lower than the peak reached in 1994. The number of births to unmarried women was up 3 percent, the highest number ever reported in the United States. However, the number of births to unmarried teenagers declined. The proportion of women who began prenatal care in the first trimester of pregnancy (83.2 percent) did not improve for 2000, nor did the rate of low birthweight (7.6 percent). The total cesarean rate rose for the fourth consecutive year to 22.9 percent, the result of both a rise in the rate of primary cesarean deliveries and a decline in the rate of vaginal births after previous cesarean delivery.
To examine perinatal outcome among singleton infants conceived with assisted reproductive technology (ART) in the United States.
Subjects were 62,551 infants born after ART treatments performed in 1996-2000. Secular trends in low birth weight (LBW), very low birth weight (VLBW), preterm delivery, preterm LBW, and term LBW were examined. Detailed analyses were performed for 6,377 infants conceived in 2000. Observed numbers were compared with expected using a reference population from the 2000 U.S. natality file. Adjusted risk ratios were calculated.
The proportion of ART singletons born LBW, VLBW, and term LBW decreased from 1996 to 2000. The proportion delivered preterm and preterm LBW remained stable. After adjustment for maternal age, parity, and race/ethnicity, singleton infants born after ART in 2000 had elevated risks for all outcomes in comparison with the general population of U.S. singletons: LBW standardized risk ratio 1.62 (95% confidence interval 1.49, 1.75), VLBW 1.79 (1.45, 2.12), preterm delivery 1.41 (1.32, 1.51), preterm LBW 1.74 (1.57, 1.90), and term LBW 1.39 (1.19, 1.59). Risk ratios for each outcome remained elevated after restriction to pregnancies with only 1 fetal heart or any of 7 other categories: parental infertility diagnosis of male factor, infertility diagnosis of tubal factor, conception using in vitro fertilization without intracytoplasmic sperm injection or assisted hatching, conception with intracytoplasmic sperm injection, conception in a treatment with extra embryos available, embryo culture for 3 days, and embryo culture for 5 days.
Singletons born after ART remain at increased risk for adverse perinatal outcomes; however, risk for term LBW declined from 1996 to 2000, whereas preterm LBW was stable.
III
To compare infant outcome after different IVF techniques.
A register study in Sweden of IVF infants compared with all infants born.
National health registers.
We studied 16,280 IVF infants, 30% of whom were conceived by intracytoplasmic sperm injection (ICSI).
None.
Multiple births, infant sex, preterm birth, low birth weight, and small for gestational age among singletons, mortality, low Apgar score, neonatal diagnoses.
Twinning was less frequent after frozen standard IVF (18.1%) and after ICSI (21.8%) than after fresh standard IVF (24.4%). The male/female ratio was significantly increased in infants conceived after standard IVF. No significant differences were seen between singleton infants conceived after different IVF methods with respect to preterm birth, low birth weight, or infant mortality, with the possible exception of frozen standard IVF, for which some of these rates were lower than after fresh standard IVF. Infants born after ICSI had an indicated lower risk of respiratory problems than infants born after standard IVF.
Little difference in outcome was seen after different IVF methods. The differences observed might be due to dissimilar characteristics of the treated women (e.g., because ICSI was mainly used in connection with male infertility).
To investigate whether the outcome of a pregnancy is related to the time required to achieve that pregnancy (TTP).
The distribution of the TTP for pregnancies ending in multiple birth, early (before week 12) and late (weeks 12-28) miscarriage, stillbirth, and extrauterine pregnancy was compared to that of pregnancies ending in singleton birth. Furthermore, the distribution of the TTP for preterm singleton births was compared to that of full-term singleton births.
Sweden.
Information from three previous studies on reproduction was used: Women chosen for exposure to persistent organochlorine pollutants, or exposure as a hairdresser, and their respective controls.
None.
Self-reported pregnancy outcome.
An increased TTP (i.e., decreased fecundability) was associated with pregnancies ending in miscarriage (early as well as late) and extrauterine pregnancies. Pregnancies ending in multiple live birth tended to have shorter TTPs than those ending in single live birth. No association between TTP and stillbirths was found. Among women whose pregnancies ended in singleton birth, a prolonged TTP was associated with preterm delivery.
The TTP of a pregnancy seemed to be associated with the outcome of that pregnancy. The mechanisms behind this phenomenon are, however, unclear.
Calculating cumulative live-birth rates from linked cycles of assisted reproductive technology (ART): data from the Massachusetts SART CORS
- J E Stern
- M B Brown
- B Luke
- E Wantman
- A Lederman
- S A Missmer
- JE Stern