[show abstract][hide abstract] ABSTRACT: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers.
We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation.
The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2).
This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363.
Human Reproduction 11/2011; 27(1):89-96. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND; Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN).
A prospective, randomized, multi-centre study was performed at four different clinics from June to December 2009. The oocyte aspiration was performed under local anaesthesia, either with a needle with a reduced diameter (0.9 mm) for the last 50 mm from the tip (RN) or with a SN (1.4 mm). A total of 257 patients were randomized (RN: n = 129; SN: n = 128). The primary endpoint was the overall pain experience self-assessed and registered by the patient on a visual analogue scale (VAS 0 mm = no pain to 100 mm = unbearable pain) immediately after the oocyte retrieval. Secondary end-points such as vaginal bleeding and several embryological parameters were also registered.
The overall pain during the oocyte retrieval procedure was significantly lower in the RN group than in the SN group (mean 21.0 mm, SD 17.5 mm and median 19.0 mm versus mean 26.0 mm, SD 19.9 mm and median 24.0 mm; P = 0.040, difference between groups mean-5.0 mm, 95% CI: 9.7 to-0.4). This was also true when adjusting for baseline characteristics such as number of follicles, number of previous oocyte pick-up, body mass index and age, by a multiple linear regression analysis. Significantly more patients (40 of 126) had less than expected vaginal bleeding in the RN group when compared with the SN group (24 of 124; 32 versus 19%; P = 0.03 and 95% CI 1.7-23.0%). No differences were found between the two needles with regard to additional i.v. analgesia, aspiration time, oocyte recovery, fertilization, cleavage rate, number of good quality embryos, number of embryos for freezing and pregnancy rate.
Oocyte aspiration performed with the newly designed thinner-tipped needle resulted in significantly less overall pain and less vaginal bleeding, without prolonging the retrieval procedure or influence the oocyte recovery rate, when compared with a SN. Clinicaltrials.gov: NCT00924885.
Human Reproduction 04/2011; 26(6):1377-83. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been claimed that the risks to the child resulting from vitrification as compared with the slow-freezing technique, may be higher owing to the high concentrations of potentially toxic cryoprotectants. We therefore retrospectively compared the obstetric and neonatal outcomes in a cohort of children born after transfer of vitrified blastocysts, fresh blastocysts and slow-frozen early cleavage stage embryos.
All children born after transfer of vitrified blastocysts (n = 106), fresh blastocysts (n = 207) and slow-frozen early cleavage stage embryos (n = 206) during the period January 2006 to May 2008 at Fertility Center Scandinavia were included. Data on obstetric and neonatal outcomes were obtained from medical records from the antenatal and delivery clinics.
For singletons, there were no significant differences between the groups in gestational age, mortality or birth defects. After adjustment for parity and BMI, birthweight was significantly higher in singletons born after transfer of vitrified blastocysts as compared with after transfer of fresh blastocysts (median 3560 versus 3510 g, P = 0.0311). More singletons born after transfer of fresh blastocysts were small for gestational age compared with singletons born after transfer of vitrified blastocysts (12.1 versus 3.0%, P = 0.0085). A higher rate of major post-partum haemorrhage was observed in the vitrified blastocyst group as compared with the other two groups (25.0 versus 6.0 and 7.5%).
No adverse neonatal outcomes were observed in children born after transfer of vitrified, as compared with fresh blastocysts or after transfer of slow-frozen early cleavage stage embryos.
Human Reproduction 07/2010; 25(7):1699-707. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo.
One hundred and seventy-three embryos diagnosed as chromosomally abnormal, 22 with no PGS result and four degenerated embryos originally diagnosed as normal were fixed and reanalysed by fluorescence in situ hybridization.
In total, 199 embryos were fixed, of which 166 were successfully reanalysed. One hundred and sixty embryos were found to be chromosomally abnormal; 48 of the reanalysed embryos with an initial diagnosis (149) had at least one cell with exactly the same chromosomal constitution shown in the first PGS analysis (34.2%). The reanalysis confirmed the initial overall chromosomally abnormal status of the embryo in 95.9% of the cases. Of all chromosomally abnormal embryos, 4.1% were diagnosed as false positive. The risk for false negative rate was at least 4.1%.
PGS seems to be a good method for selecting against chromosomally abnormal embryos but not for determining an embryo's exact chromosomal constitution.
Human Reproduction 08/2009; 24(11):2960-4. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Advanced maternal age (AMA) is an important parameter that negatively influences the clinical pregnancy rate in IVF, in particular owing to the increased embryo aneuploidy rate. It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate. The purpose of this study was to test whether employing preimplantation genetic screening (PGS) in AMA patients would increase the clinical pregnancy rate.
We conducted a two-center, randomized controlled trial (RCT) to analyze the outcome of embryo transfers in AMA patients (>or=38 years of age) after PGS using FISH analysis for chromosomes X, Y, 13, 16, 18, 21 and 22. The PGS group was compared with a control group. The primary outcome measure was clinical pregnancy rate after 6-7 weeks of gestation per randomized patient.
The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome. Of the 320 patients calculated to be included in the study, 56 and 53 patients were randomized into the PGS and control groups, respectively. The clinical pregnancy rate in the PGS group was 8.9% (95% CI, 2.9-19.6%) compared with 24.5% (95% CI, 13.8-38.3%) in the control group, giving a difference of 15.6% (95% CI, 1.8-29.4%, P = 0.039).
Although the study was terminated early, this RCT study provides evidence against the use of PGS for AMA patients when performing IVF. Trial registration number: ISRCTN38014610.
Human Reproduction 06/2008; 23(12):2806-12. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: A prospective randomized study was carried out in two centres to compare the number of oocytes retrieved after two different starting doses of recombinant human FSH (rhFSH) (Gonal-F) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI) cycles using the multiple dose regimen of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix (Cetrotide) to prevent induction of the premature LH surge.
Sixty women were randomized to receive rhFSH 150 IU ('low'), and 60 women to receive rhFSH 225 IU ('high') as the starting dose for the first 5 days of stimulation. From stimulation day 6 and onwards, including the day of human chorionic gonadotrophin (HCG) administration, the women received 0.25 mg of cetrorelix as a daily dose. The primary endpoint was the number of oocytes retrieved.
The mean number (+/- SD) of oocytes was 9.1 +/- 4.4 and 11.0 +/- 4.6 in the 'low' and 'high' groups respectively (P = 0.024). The mean number of 75 IU ampoules of rhFSH was significantly lower in the 'low' group (23.0 +/- 6.3 versus 30.5 +/- 5.6, P < 0.0001). The ongoing pregnancy rate per started cycle and per embryo transfer were 25.9 and 28.8% versus 25.4 and 26.8% respectively in the 'low' and 'high' rhFSH groups (P = NS).
When using a starting dose of 225 IU rhFSH combined with the multiple dose of 0.25 mg cetrorelix from stimulation day 6, significantly more oocytes were obtained than with a starting dose of 150 IU rhFSH.
Human Reproduction 09/2001; 16(8):1676-81. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups.
Human Reproduction 07/1999; 14(6):1440-4. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: The study compares treatment outcome and costs of ovulation induction cycles and in vitro fertilization cycles in infertile women with clomiphene resistant polycystic ovary syndrome.
Twenty-eight infertile women with clomiphene resistant polycystic ovary syndrome referred to a university clinic were prospectively randomized to ovulation induction or in vitro fertilization. Forty-one ovulation induction cycles and thirty in vitro fertilization cycles were performed. Mann-Whitney U-test was used for between group comparisons and frequencies were compared with Fisher's exact test.
More pregnancies per completed cycle were noted in the in vitro fertilization group than in the ovulation induction group. Drug costs were not much higher in the in vitro fertilization group but treatment costs were higher due to the additional costs of ovum pick up and embryo transfer. The cost per pregnancy was about twice as high in the ovulation induction group as in the in vitro fertilization group. The cost per term pregnancy including delivery was 1.6 times higher in the ovulation induction group.
For a group of obese women with clomiphene resistant polycystic ovary syndrome, in vitro fertilization seems a cost-effective treatment.
[show abstract][hide abstract] ABSTRACT: To study whether there is an increased risk of glucose intolerance and hypertensive complications during pregnancy in women with polycystic ovary syndrome (PCOS) and if there is an adverse pregnancy outcome.
In a retrospective case-control study, pregnancies and neonatal outcome were compared in 33 women with PCOS and 66 women without PCOS. The women were treated at Huddinge University Hospital; antenatal care was given at associated outpatient units.
Blood glucose and blood pressure during the different trimesters. Pregnancy outcome in terms of gestational length, birth weight, and need for neonatal intensive care.
No significant differences were found in blood glucose levels between the groups. There were also no differences in blood pressure during the first and second trimester. However, during the third trimester and labor, the PCOS group had a significantly higher blood pressure than the control group. Apart from a tendency toward reduced growth of twins in PCOS mothers, the babies were healthy, overall, with few problems in the neonatal period.
No major differences with regard to perinatal outcome in pregnant women with and without PCOS were found. An increased risk of hypertensive disorders in the third trimester and during labor was demonstrated in the PCOS group. This suggests that in the antenatal care of women with PCOS, attention should focus on blood pressure in order to reduce the risks of morbidity associated with hypertension.
Hypertension in Pregnancy 02/1999; 18(1):73-80. · 0.93 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have tested and subsequently successfully applied a single-needle approach to obtain blastomere biopsies from human preimplantation embryos for preimplantation genetic diagnosis (PGD). The method was first evaluated in a mouse system and shown to be compatible with a high degree of in vitro and in vivo development of biopsied mouse embryos. Furthermore, we showed that biopsied mouse embryos after transfer to recipient mice underwent implantation, normal development and delivery. Litters were followed through puberty and adulthood and shown to be normal with regard to sexual function and also a panel of biochemical and morphological parameters including organ histology. Successful human preimplantation diagnosis, followed by pregnancies and birth of healthy babies, was established with two out of three couples carrying a risk to transmit chromosomal abnormalities leading to severe disease. This is the first report of the successful use of a single-needle approach in human PGD. Considering its simplicity, we conclude that the single-needle approach is an attractive alternative for biopsies in PGD.
[show abstract][hide abstract] ABSTRACT: The aim of this retrospective study was to compare the outcome of in vitro fertilization and embryo transfer in women with endometriosis and a control group with tubal-factor infertility.
Forty-eight patients with endometriosis underwent 65 cycles of in vitro fertilization and embryo transfer at Huddinge University Hospital. The matched control group with tubal-factor infertility consisted of 98 cycles in 98 patients. These groups were retrospectively analyzed regarding stimulation, fertilization, embryo development, implantation, and pregnancy outcome.
The fertilization rate was significantly lower in women with endometriosis, but the cleavage, implantation, and pregnancy rates did not differ.
Our results show that women with endometriosis have a lower fertilization rate compared with women with tubal-factor infertility. However, once the oocyte is fertilized, it seems that the preembryo has a normal chance of implantation, leading to similar pregnancy rates.
Journal of Assisted Reproduction and Genetics 11/1998; 15(9):530-4. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Percutaneous epididymal sperm aspiration (PESA) for retrieval of spermatozoa for intracytoplasmic sperm injection (ICSI) is a new simplified technique in the treatment of men with obstructive azoospermia. There has been a fear that the PESA procedure, being blind, could cause damage to the epididymal duct system and make it impossible to retrieve spermatozoa if a repeated procedure is required. We report here on repeated PESA procedures from the same unilateral epididymis. Twenty-seven men with obstructive azoospermia were investigated retrospectively regarding sufficiency of the number of motile spermatozoa for ICSI, fertilization rate (FR) and possibility of collecting spermatozoa for cryopreservation in repeated PESA procedures. Sufficient motile spermatozoa for ICSI were found in a similar proportion of men at the first two attempts: 91 and 89% respectively. Fertilization rate and the possibility of collecting spermatozoa for cryopreservation were also similar at the first two PESA procedures: 62 versus 67% and 33 versus 33% respectively. At the third procedure, motile spermatozoa for ICSI were retrieved in 86% (6/7), FR was 47% and spermatozoa were cryopreserved in one case. Two men underwent a fourth PESA. In both cases, a sufficient number of motile spermatozoa for ICSI was found and FR was 62%. This study shows that in men with obstructive azoospermia, PESA can be repeated on the same unilateral epididymis up to three times, with good opportunity of retrieving sufficient motile spermatozoa for ICSI.
Human Reproduction 11/1998; 13(1O):2805-7. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report the first case of preimplantation genetic diagnosis used in order to avoid chromosomal imbalance in the progeny of a woman mildly affected by DiGeorge syndrome and carrier of a microdeletion of chromosome 22q11.2. In total, seven embryos were biopsied in three separate treatments and analysed by fluorescent in-situ hybridization (FISH). Of these, four were carrying the deletion, two were normal and in one the analysis was inconclusive. The diagnostic procedure was performed within 5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred in the third treatment, but no pregnancy was established. Patients with a 22q11 microdeletion, who have a 50% risk of transmitting the deletion to their offspring, can now be offered preimplantation genetic diagnosis using FISH for the detection of a 22q11 deletion.
Molecular Human Reproduction 10/1998; 4(9):871-5. · 4.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: We report the first established pregnancy using preimplantation genetic diagnosis in order to avoid chromosomal imbalance in the progeny of a woman carrying a large inversion of chromosome 5. This is also the first time where it has been possible to study the distribution of balanced and unbalanced gametes in a female inversion carrier. In total, 23 embryos were biopsied in two separate treatments and analysed by fluorescent in-situ hybridization. Of these, 10 were unbalanced, nine were balanced and for four the analysis was inconclusive. The diagnostic procedure was performed within 3.5 h. This allowed the biopsied embryos to be transferred the same day as the biopsy was taken (day 3). Two embryos were transferred each time, and in the second treatment a twin pregnancy with two chromosomally balanced fetuses was established. Healthy twins were delivered at 34 weeks of gestation.
Molecular Human Reproduction 08/1998; 4(7):719-23. · 4.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Open testicular biopsy is a classic method of investigation in men with azoospermia. Recently, percutaneous needle biopsy of the testis has been used in attempts to obtain material for histopathological diagnosis in such cases and to retrieve spermatozoa for intracytoplasmic sperm injection (ICSI). To determine whether a 19 gauge (G) and a 21G butterfly needle could be used for percutaneous aspiration of testicular tissue to determine the presence of mature spermatids and assess spermatogenesis, 10 patients (16 testes) and 12 patients (17 testes) underwent 19G or 21G needle biopsy respectively, immediately followed by open testicular biopsy, with both procedures under local anaesthesia. Biopsy with each needle size was compared with open biopsy. With the 19G needle, in the 14 cases where material was obtained there was full agreement with open biopsy regarding the presence or absence of mature spermatozoa, whereas with the 21G needle only nine of the 13 biopsies yielding material were predictive in this respect. Each needle size correlated poorly with open biopsy regarding evaluation of spermatogenesis. We conclude that percutaneous biopsy with a 19G butterfly needle is a quick and reliable method for demonstrating spermatozoa for ICSI. But for a detailed histopathological diagnosis, however, the needle biopsies gave poor results, whereas the material from the open testicular biopsies was assessable.
Human Reproduction 06/1998; 13(5):1266-71. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Treatment of testicular cancer (TC) may cause infertility due to reduced sperm quality with or without an ejaculation problem. In cases of anejaculation or retrograde ejaculation, spermatozoa can be obtained by transrectal electroejaculation (TE) or testicular sperm extraction (TESE) and used for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In this study, 15 out of 17 couples evaluated for infertility after TC, underwent a total of 21 treatment cycles, resulting in 18 embryo transfers. Spermatozoa were obtained by TE in 16 cycles, by masturbation in three cycles and by TESE in one. In one cycle no spermatozoa were found using TESE. Fertilization and cleavage was achieved by IVF in seven cycles and ICSI in 11 cycles; average fertilization rates of 57 and 55% respectively were observed. Twelve clinical pregnancies occurred, of which 11 have been delivered or are ongoing. The ongoing pregnancy rate was 57% per cycle. These results show that infertility after testicular cancer can be treated effectively with IVF and that ICSI even permits treatment of patients who have severe oligozoospermia.
Human Reproduction 03/1998; 13(2):414-8. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is often associated with hyperinsulinaemia and peripheral insulin resistance. Whether the ovary is resistant to insulin is a matter of controversy. The aim was therefore to study the effect of insulin on lactate accumulation, an indicator of glucose metabolism, in granulosa-luteal cells from women with PCOS and from women with normal ovarian function. The cells were obtained from women undergoing clinical in-vitro fertilization-embryo transfer, either from patients with normal ovarian function and tubal or male infertility, or from women with PCOS, with or without tubal factor. The patients were down-regulated with buserelin and stimulated with urofollitrophin and human chorionic gonadotrophin (HCG). Follicle aspiration was performed under ultrasound guidance. Following oocyte recovery the granulosa-luteal cells were isolated, washed and cultured (2-3 x 10(4) viable cells/well) in serum-free Eagle's minimal essential medium for 48 h. After washing, the cells were then cultured in medium containing HCG (0.1-10 IU/ml) or insulin (0.05-0.5 microg/ml) for 24-48 h. Lactate accumulation in the media and cellular protein were analysed. Basal lactate accumulation did not differ in granulosa-luteal cells obtained from normal or PCOS ovaries, and averaged 46 and 49 nmol/g protein/24 h, respectively. A significant stimulation (40-60%) was obtained by HCG in both groups. Insulin caused a dose-dependent increase in lactate in granulosa-luteal cells obtained from normal ovaries (control: 45.5 +/- 6.3; insulin 0.5 microg/ml: 77 +/- 10 nmol/microg protein). Lactate accumulation in granulosa-luteal cells from PCOS ovaries was not altered in the presence of insulin. These results suggest that granulosa-luteal cell glucose metabolism is resistant to insulin in PCOS.
Human Reproduction 12/1997; 12(11):2469-72. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently pure gonadotropins have become available through recombinant technology. In parallel with ongoing clinical trials it is important to examine the effects of these new gonadotropin preparations in experimental studies in human granulosa cells. In the present study the effects of recombinant FSH (rFSH) and LH (rLH) on steroid and inhibin production were examined in human granulosa cells in culture.
Granulosa cells were obtained during the follicular phase of the menstrual cycle in seven women undergoing gynecological laparotomy and from follicles in stimulated cycles in women undergoing oocyte retrieval in connection with in vitro fertilization/embryo transfer. The granulosa cells were cultured in modified Medium 199 containing 1% fetal bovine serum for 4-8 days with and without hormones. Media were changed on alternate days and stored at -20 degrees C until analyzed for estradiol, progesterone and inhibin.
Granulosa cells from natural cycles were highly responsive to rFSH which caused a dose-related (rFSH 0.1 to 100 ng/ml) increase in estradiol and progesterone accumulation. The maximal stimulatory effect was reached with a concentration of rFSH between 1 and 10 ng/ml. Granulosa cells from stimulated cycles responded highly to rLH in terms of increased progesterone production during the whole culture period. A maximal stimulatory effect was observed with rLH at a concentration of 0.1 ng/ml. Both types of granulosa cells responded to recombinant gonadotropins in terms of increased inhibin production.
The present study demonstrates that granulosa cells from human ovarian follicles are highly responsive to recombinant gonadotropins as demonstrated by increased steroid and inhibin production.
European Journal of Endocrinology 07/1997; 136(6):617-23. · 3.14 Impact Factor