Laurel Stadtmauer

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

OBJECTIVE To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). DESIGN Retrospective data analysis of selective groups of patients. SETTING A private IVF unit. PATIENT(S) Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. INTERVENTION(S) In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. MAIN OUTCOME MEASURE(S) Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycles E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). RESULT(S) In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S) Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.

High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization-embryo transfer

OBJECTIVE To compare the pregnancy outcomes during IVF-ET when different dosages of hMG are used after follicular phase suppression with leuprolide acetate (LA). DESIGN Retrospective chart review. SETTING Hospital-based IVF-ET program. PATIENTS From January 1990 to December 1992, 264 cycles reached ET after LA downregulation and gonadotropin stimulation. RESULTS Higher doses of gonadotropins, as measured by both average daily dose and total dose per cycle, were associated with lower clinical pregnancy rates. This effect was independent of age, basal FSH level, endometrial thickness, maximal E2 levels, number of eggs retrieved, and embryos transferred. CONCLUSION High dosages of exogenous gonadotropins are associated with lower pregnancy rates in IVF-ET.

Impact of Polycystic Ovary Syndrome on Selected Indicators of In Vitro Fertilization and Intracytoplasmic Sperm Injection Treatment Success

OBJECTIVES To examine the effect of polycystic ovary syndrome (PCOS), a marker of the metabolic syndrome, on selected indicators of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment success. METHODS A retrospective cohort study was conducted using existing data on 69 IVF/ICSI treatment cycles undergone by PCOS women and a caliper-matched sample of 69 IVF/ICSI treatment cycles undergone by non-PCOS women over a 7-year period at a major fertility treatment center. Matching criteria were age and date at IVF/ICSI treatment initiation. Process and outcome measures were used to define successful IVF/ICSI treatment. Statistical significance was determined at an alpha level of 0.05. RESULTS The total number of oocytes and the number of immature oocytes retrieved in the process of an IVF/ICSI cycle were significantly higher in the context of PCOS. No significant differences were observed among PCOS and non-PCOS groups on various IVF/ICSI cycle outcomes, including high-grade embryo, pregnancy achievement, miscarriage, and live birth status. CONCLUSIONS Although IVF/ICSI yields more oocytes in the context of PCOS, IVF/ICSI outcomes do not differ significantly by PCOS status. Prospective cohort studies are needed to examine short-term and long-term health effects of PCOS in the context of IVF/ICSI.

CHAPTER 27 – The Ovarian Factor in Assisted Reproductive Technology

This chapter addresses the role of the ovary in assisted reproductive technology (ART), the organ with the largest impact on ART success. It describes the decline in fertility with age and the relationship between increased aneuploidy and decreased oocyte quality and ovarian reserve. It also discusses ovarian stimulation, specifically the approach to low responders, hyperresponders, and the role of luteinizing hormone (LH) in ovarian stimulation. Assisted reproductive technology (ART) has become increasingly prevalent each year, with more than 360 ART programs available in 1999 and more than 88,000 cycles in the United States alone. In oocyte donor programs, rates were higher with a delivery rate per transfer of 41%, which is consistent with early research that showed higher success rates for older patients using oocytes from young donors. Therefore, the most important factor for the success of ART is oocyte quality, which is affected by ovarian age, whereas the age of the endometrium is less important. The biggest challenge continues to be treating women of advanced reproductive age who wish to use their own eggs.

Timing of Oocyte Retrieval and Embryo Transfer with Pregnancy Duration

BACKGROUND Recent studies have suggested that assisted reproductive technology (ART) may be associated with a shorter pregnancy duration, possibly due to various aspects of the ART procedure. The purpose of this study was to examine whether pregnancy duration is affected by timing of oocyte retrieval and embryo transfer with respect to the first day of the last menstrual period (LMP) among pregnancies achieved through in vitro fertilization with or without intracytoplasmic sperm injection. METHODS A retrospective study was conducted at an academic center in Norfolk, Virginia, with analyses based on 294 ART cycles. RESULTS Median and interquartile range for pregnancy duration was estimated at 38.2 ± 3.4 weeks. Similarly, median and interquartile ranges for days between LMP and day of oocyte retrieval (27.0 ± 2.0) and between LMP and embryo transfer (29.8 ± 2.2) differed significantly from the standard of 14 days. Timing of oocyte retrieval and embryo transfer with respect to LMP were accelerated among multiple compared with single gestations. For single gestations, pregnancy duration was positively associated with time duration between LMP and embryo transfer (β=0.14, p=0.036). The number of days between oocyte retrieval and embryo transfer was marginally associated with a shorter pregnancy duration in women with multiple gestations (β=3.70, p=0.083). Controlling for patient characteristics, timing of oocyte retrieval and embryo transfer were not significantly associated with pregnancy duration. CONCLUSIONS With few exceptions, timing of oocyte retrieval or embryo transfer did not affect pregnancy duration among ART-conceived live births.