BackgroundBoth oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate.MethodsBetween January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation.ResultsPretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups.ConclusionsThis is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated.Trial registrationClinicalTrials.gov http://NCT01501448.
Endometriosis affects 6 to 10% of reproductive-age women. 1 The prevalence of this condition in women experiencing pain, infertility, or both is as high as 35 to 50%. 2 The monthly fecundity rate in couples diagnosed with both endometriosis and infertility is between 2% and 10% per month, 3 whereas it is 25 to 30% for normal couples of reproductive age for the first three cycles. It declines to 4% when couples have been trying to conceive for >1 year. 4 Even minimal endometriosis may be associated with marked subfertility. 5 Outcomes of in vitro fertilization (IVF) cycles performed in women with endometriosis are significantly worse than in patients without this condition, 6-9 although some authors report that these differences are only observed in patients with endometriomas. 10 Impaired parameters include the number of oocytes retrieved, peak E2 (estradiol) concentration, fertilization rate, pregnancy rate (PR), and implantation rate (IR). 11 Some investigators suggest an altered embryo quality, 6,12 possibly due to aberrant events in morphological embryogenesis 13 or a higher in vitro embryo blockage in patients with endometriosis. 14 The impact of endometriosis on ovarian reserve and the quality of retrieved oocytes seems evident. Lower IR, however, raises the obvious question whether this finding is purely the consequence of poorer embryo quality or number, or whether it also reflects compromised endometrial receptivity.
Keywords► endometriosis ► oocyte donation ► endometrial receptivity
AbstractOutcomes of in vitro fertilization cycles in women with endometriosis are significantly worse than in patients without this condition. The impact of endometriosis on ovarian reserve and the quality of retrieved oocytes seems evident. Lower implantation rates, however, raise the question whether this finding is purely the consequence of lower number and poorer quality of embryos, or whether it also reflects compromised endometrial receptivity. Oocyte donation provides an interesting model to investigate reproductive outcome because factors affecting the oocytes are excluded, especially if cycles using oocytes derived from the same donor are analyzed. These studies have shown lower implantation rates in nonendometriotic patients who received oocytes from women with endometriosis, whereas healthy donated oocytes have proven to contribute to a pregnancy with similar chances in women without the disease. The question still to be answered is whether this situation applies for natural cycles or whether it is the use of gonadotropin-releasing hormone analogs and hormonal replacement therapy used for endometrial priming in oocyte recipients that reestablishes an adequate uterine environment. Using a genomic tool based on microarray technology (endometrial receptivity array), the study of differential gene expression in the eutopic endometrium of endometriosis patients undergoing oocyte donation treatment is still underway.Issue Theme Ramifications and Adaptations to Endometriosis-Induced Infertility; Guest Editor, Dan I. Leb...
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