[Show abstract][Hide abstract] ABSTRACT: To assess ovarian reserve after methotrexate treatment for ectopic pregnancy or pregnancy of unknown location after assisted reproductive technology (ART).
Retrospective cohort study.
Large ART practice.
Women receiving methotrexate or surgery after ART.
Follicle-stimulating hormone (FSH), antral follicle count (AFC), and oocyte yield compared between women treated with methotrexate or surgery, with secondary outcomes of clinical pregnancy and live birth.
There were 153 patients in the methotrexate group and 36 patients in the surgery group. Neither group demonstrated differences in ovarian reserve or oocyte yield in a comparison of the before and after treatment values. The change in ovarian reserve and oocyte yield after treatment were similar between the two groups. The number of doses of methotrexate was not correlated with changes in ovarian reserve, indicating no dose-dependent effect. Time between treatment and repeat ART was not correlated with outcomes. Live birth in subsequent cycles was similar in the two groups.
Ovarian reserve and subsequent ART cycle outcomes were reassuring after methotrexate or surgical management of ectopic pregnancy. No adverse impact of methotrexate was detected in this large fertility cohort as has been previously described elsewhere.
Fertility and sterility 11/2013; · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of luteal phase P support after ovulation induction IUI.
A systematic review and meta-analysis.
Undergoing ovulation induction IUI.
Any form of exogenous P in ovulation induction IUI cycles.
Clinical pregnancy and live birth.
Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67).
Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction.
Fertility and sterility 07/2013; · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As fertility rates among women of advanced reproductive age have steadily increased, so has the utilization of fertility services. National health policies provide infertility treatment coverage in several developed countries; however, in the United States infertility treatment is largely privately funded, resulting in limited access to care. In response to the lack of insurance coverage, many practices offer fertility treatment on a risk-sharing or contingency fee basis. The ethical delivery of care under the auspices of these programs requires adherence to core principles including transparency, patient autonomy, and the delivery of appropriate medical care. Moreover, concerns regarding patient understanding and decision making have also been of foremost concern. Patients must be able to fully appreciate the financial and clinical implications of contingency fee programs. To further explore patient comprehension and satisfaction, we surveyed participants in our shared risk assisted reproductive technology program. The overwhelming majority of respondents felt adequately informed of and fairly charged for their treatment. Our results demonstrate that shared risk programs can receive strong endorsement from participants, which may lead to improved utilization of and perseverance with fertility treatment.
Seminars in Reproductive Medicine 05/2013; 31(3):198-203. · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To estimate the effect of the embryo stage, trophectoderm (TE) morphology grade, and inner cell mass (ICM) morphology grade on live birth in single-blastocyst transfers. DESIGN: Retrospective cohort study. SETTING: Large private assisted reproductive technologies (ART) practice. PATIENT(S): Fresh autologous ART cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): A total of 694 single-blastocyst transfers met the inclusion criteria. Univariate regression analysis showed embryo stage and TE score to be correlated with implantation and live birth. Live birth rates were 57%, 40%, and 25% for TE grades A, B, and C, respectively. There was no significant association between ICM grade and implantation or live birth. Live birth rates were 53%, 52%, and 0% for ICM grades A, B, and C respectively. Multiple logistic regression analysis showed that only patient age and TE grade were significantly associated with implantation and live birth, whereas ICM grade was not significantly associated with outcome. The TE score had the strongest correlation with live birth. CONCLUSION(S): TE grading, but not ICM grading, significantly correlated with implantation and live birth for single-blastocyst transfers.
Fertility and sterility 01/2013; · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: STUDY QUESTION: Does follicular flushing during assisted reproductive technologies (ART) improve the number of oocytes retrieved? SUMMARY ANSWER: Follicular flushing during ART does not result in a greater number of oocytes in normal responders. WHAT IS KNOWN ALREADY: Despite limited evidence supporting the use of follicular flushing, it continues to be a common procedure in many ART clinics. Prior studies have provided conflicting results regarding the routine use of flushing during oocyte retrieval. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis of 518 patients who participated in 6 randomized trials over 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Literature searches were conducted to retrieve randomized controlled trials on follicle or ovarian flushing in ART. Databases searched included PubMed, EMBASE, Web of Science and the Cochrane Database of Clinical Trials (CENTRAL). Six trials that included 518 subjects matched the inclusion criteria. Studies included were limited to trials that were published, randomized trials comparing oocyte retrieval with a single-lumen pick-up needle versus follicle flushing after direct aspiration with a multi-channel oocyte pick-up needle in ART patients. MAIN RESULTS AND THE ROLE OF CHANCE: In each of the trials, measures of the oocyte yield (oocytes retrieved divided by follicles aspirated), total oocytes retrieved, fertilization or pregnancy were not different when comparing direct aspiration with follicle flushing. Four trials reported a higher operative time with follicle flushing. Results of the meta-analysis indicated no significant differences in the oocytes retrieved [weighted mean difference: 0.07, 95% confidence interval (CI): -0.13 to 0.29] or the oocyte yield (odds ratio: 1.06, 95% CI: 0.95-1.18) between the non-flushing and flushing groups. LIMITATIONS, REASONS FOR CAUTION: All trials featured an open label design and the majority of patients in this meta-analysis were normal responders. The applications of these results to poor responders, patients undergoing natural cycle ART or minimal stimulation ART should be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Follicle flushing does not improve ART outcomes in normal-responding patients and should not be performed. This meta-analysis should solidify this recommendation as it includes the largest trial published on the subject and is consistent with a recently published Cochrane review. STUDY FUNDING/COMPETING INTEREST(S): This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
Human Reproduction 05/2012; 27(8):2373-9. · 4.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A review of the scientific literature on the use of exogenous LH in assisted reproductive technology was performed by searching the MEDLINE, PubMed and Cochrane online databases. Scientific evidence was reviewed comparing recombinant FSH-only protocols to protocols supplemented with exogenous LH activity: human menopausal gonadotrophin (HMG), recombinant LH and mid-follicular human chorionic gonadotrophin (HCG). Studies were further compared based on pituitary suppression with gonadotrophin- releasing hormone (GnRH) antagonist and agonist protocols. Primary focus was given to randomized controlled trials and meta-analyses. Data from hypogonadotrophic hypogonadal patients demonstrated the importance of LH activity for success of assisted reproduction treatment. However, the majority of normogonadotrophic patients had adequate endogenous LH to successfully drive ovarian steroidogenesis and oocyte maturation. Exogenous LH supplementation was consistently associated with higher peak oestradiol concentrations. The use of HMG in long GnRH agonist cycles was associated with a 3–4% increase in live birth rate. There was insufficient evidence to make definitive conclusions on the need for exogenous LH activity in GnRH antagonist cycles or the benefit of recombinant LH and HCG protocols. Poor responders and patients 35 years of age and older may benefit from exogenous LH.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age.
A systematic review and meta-analysis.
Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age.
Patients 35 years and older undergoing assisted reproduction.
Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles.
Implantation and clinical pregnancy.
Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83).
The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age.
Fertility and sterility 02/2012; 97(5):1108-14.e1. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign metastasizing leiomyoma and lymphangioleiomyomatosis (LAM) both are characterized by abnormal proliferation of smooth muscle-like cells in the lung.
A 32-year-old African woman with a diagnosis of LAM underwent myomectomy for uterine leiomyomas. An alternative diagnosis of benign metastasizing leiomyoma was made on repeat lung biopsy. Treatment with leuprolide acetate decreased pulmonary infiltrates and improved lung function and exercise tolerance.
Accurately diagnosing benign metastasizing leiomyoma has important implications for clinical outcome. Because its clinical presentation may be misleading, immunohistochemical techniques may assist in differentiating benign metastasizing leiomyoma from LAM. This is important because, in benign metastasizing leiomyoma, reduced tumor burden and improved pulmonary function may be achieved by suppressing gonadal steroids.
[Show abstract][Hide abstract] ABSTRACT: Shared Risk programs require adherence to core principles: transparency, patient autonomy, and appropriate medical care. These programs improve utilization of and perseverance with fertility treatment, receiving strong patient endorsements.
Fertility and sterility 06/2011; 95(7):2198-9. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare methylation profiles and expression levels of Brahma at different stages of spermatogenesis, and to identify the methylation pattern during oogenesis, we analyzed gene expression and methylation patterns in murine germ cells at various developmental stages. The methylation levels of CpG islands within Brahma increased during spermatogenesis and decreased during oogenesis. This change in methylation pattern correlates with the change in expression of Brahma during spermatogenesis. As the degree of methylation increases, the expression decreases. The change in methylation is opposite during oogenesis, which suggests opposite expression levels.
Fertility and sterility 01/2011; 95(1):382-4. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the relationship between male age and pregnancy outcome in donor oocyte assisted reproductive technology cycles.
Private IVF center.
A total of 1,392 donor cycles from 1,083 female recipients and their male partners.
Oocyte donor cycles.
Increasing male age was associated with semen parameters including volume and motility; however, male age was not observed to have a statistically significant association with likelihood of live birth in donor cycles after adjustment for female recipient age.
When treatment cycle number and female recipient age were taken into account, male age had no significant association with pregnancy outcomes in assisted reproductive technology donor cycles in this study population.
Fertility and sterility 01/2011; 95(1):147-51. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine cycle outcomes among patients demonstrating an attenuated ovarian response that proceeded to oocyte retrieval to those converted to intrauterine insemination (IUI).
Retrospective cohort study.
Large private fertility center.
First planned autologous assisted reproductive technology (ART) cycles among women demonstrating a poor ovarian response to hyperstimulation (≤4 follicles≥14 mm, peak E2<1,000 IU/L at hCG administration).
Oocyte retrieval or IUI conversion.
Live birth and clinical pregnancy.
A total of 269 IUI conversions and 167 oocyte retrievals followed a poor ovarian response to gonadotropins among first planned ART cycles. Number of follicles≥14 mm (2.3 vs. 3.5) and peak E2 levels (555 vs. 743 pg/mL) were lower for IUI conversions compared with those proceeding to ART. Peak E2 was similar between groups after adjusting for follicle number (IUI: 611 pg/mL; ART: 652 pg/mL). Stimulation response was similar between treatment groups with equivalent follicle numbers. Undergoing oocyte retrieval was associated with significantly improved pregnancy (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.8-7.4) and live birth outcome (OR 3.5, 95% CI 1.7-8.0) after adjusting for age and follicle number.
Among women demonstrating a poor ovarian response to gonadotropins, proceeding with planned ART resulted in significantly higher pregnancy rates than converting these cycles to IUI.
Fertility and sterility 11/2010; 94(6):2073-7. · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Progesterone is critical for secretory endometrial differentiation in women, but its downstream mediators are poorly understood.
Our objective was to investigate endometrial expression of Indian Hedgehog (IHH) and genes involved in its signaling [smoothened (SMO), patched-1 (PTCH1), glioma-associated oncogene homolog 1 (GLI1), and GLI2] during the menstrual cycle and the effects of the selective progesterone receptor modulator CDB-2914 on its expression.
Comparisons between normally cycling volunteers and women with symptomatic fibroids who received CDB-2914 or placebo were made at a clinical research center.
Endometrial biopsy was performed on 34 volunteers, 17 additional women with fibroids.
Endometrial expression of IHH, SMO, PTCH1, GLI1, and GLI2 by in situ hybridization and/or RT-PCR and IHH, GLI1, and PTCH1 immunohistochemistry were evaluated.
RT-PCR showed expression of IHH, SMO, PTCH1, GLI1, and GLI2, with significant increases in IHH (5.2-fold) and GLI1 (3.6-fold) in endometrium exposed to CDB-2914 compared with placebo. In situ hybridization showed IHH mRNA expression in glands and stroma that was stronger in secretory samples. Among volunteers, IHH and GLI1 immunohistochemistry scores were higher in the secretory than proliferative phase in the nuclei and cytoplasm of glands and stroma (P=0.0002-0.04). Compared with follicular-phase controls, women exposed to CDB-2914 showed increased IHH expression in all compartments except stromal cytoplasm (P=0.0199-0.0423); GLI1 was up-regulated in glandular nuclei and cytoplasm compared with both volunteers and women receiving placebo (P≤0.0416).
The temporal increase in endometrial IHH and GLI1 during the secretory phase, and their modulation by CDB-2914, suggests progestin regulation and a potential role in endometrial differentiation and implantation.
The Journal of Clinical Endocrinology and Metabolism 09/2010; 95(12):5330-7. · 6.31 Impact Factor