Non-inferiority of progestin-primed ovarian stimulation versus GnRH antagonist protocol: A propensity score-weighted analysis.

PURPOSE: To evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. METHODS: In this retrospective cohort study, we included 804 patients who were treated between January 1st, 2022, and July 1st, 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos. RESULTS: Baseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. CONCLUSIONS: The PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

Phase IV, open-label, randomized study of low-dose recombinant human follicle-stimulating hormone protocols for ovulation induction.

BACKGROUND: This Phase IV, open-label, multicentre, randomized study (MEnTOR) compared two low-dose recombinant human follicle-stimulating hormone (r-hFSH) protocols for ovulation induction. METHODS: This study was conducted in six Middle Eastern countries between March 2009 and March 2011. Eligible women (18-37 years), with World Health Organization Group II anovulatory infertility, were randomized to receive r-hFSH (starting daily dose: 75 IU) as a chronic low-dose (CLD) (37.5 IU dose increase on Day 14) or low-dose (LD) (37.5 IU dose increase on Day 7) protocol if no follicles were ≥ 10 mm. The maximum r-hFSH daily dose permitted was 225 IU/day. The total length of ovarian stimulation could not exceed 35 days, unless ultrasound assessment suggested imminent follicular growth and maturation. Patients underwent only one treatment cycle. Primary endpoint: incidence of mono-follicular development. Secondary endpoints included: stimulation duration and rates of bi-follicular development; human chorionic gonadotrophin administration rate; clinical pregnancy; and cycle cancellation (owing to inadequate response). Adverse events (AEs) were recorded. The primary efficacy analysis was performed using data from all patients who received at least one dose of correct study medication, had at least one efficacy assessment, and no protocol violations at treatment start (CLD group, n=122; LD group, n=125). RESULTS: Mono-follicular development rates (primary endpoint) were similar in both groups (CLD: 56.6% [69/122] versus LD: 55.2% [69/125], p=0.93; primary efficacy analysis population). Similarly, there were no significant differences between groups in bi-follicular development, clinical pregnancy or cycle cancellation (inadequate response) rates. In patients who received human chorionic gonadotrophin injections, the mean duration of stimulation was 13.7 days in the CLD group and 12.9 days in the LD group. Clinical pregnancy rates for those patients who received an hCG injection were similar in both groups (CLD: 20.2% [19/94] versus LD: 19.8% [18/91], p=0.94; primary efficacy analysis population). Most AEs were mild in severity. Only one case of ovarian hyperstimulation syndrome was reported (mild; CLD group). CONCLUSIONS: Efficacy and safety outcomes were similar for the two protocols.

Impact of high serum progesterone during the late follicular phase on IVF outcome.

With ovarian stimulation for IVF, serum progesterone concentration may increase during the last few days of stimulation. Several factors, mainly the intensity of the ovarian response to gonadotrophins, have been identified to explain progesterone elevation but many other issues remain uncertain. The aim of this narrative, nonsystematic review is to address the nonconsensual issues of the reasons and consequences of premature progesterone elevation during ovarian stimulation. The determination of the optimal threshold above which progesterone elevation may have an impact on IVF outcome is still a matter of debate because it is likely related to the patient's profile. Additionally, it is still uncertain whether the duration of progesterone elevation negatively affects IVF outcome. Recommendations for both prevention and management of progesterone elevation are here suggested by a group of experts. Nevertheless, before being implemented in clinical practice, they require new assessment through additional clinical trials.

Subtle perturbations of ovarian steroidogenesis in patients classified as Poseidon Group 3. Which consequences for therapeutic strategy?

The optimal strategy for stimulation of young women with a low ovarian reserve is still a challenging issue because the physio-pathogeny of this disorder is often unknown. As androgen production by the ovary plays a crucial role in folliculogenesis, it was tempting to speculate that subtle perturbations in ovarian steroidogenesis might participate to the low responsiveness to gonadotrophins. Indeed, in vitro analysis of human luteinized granulosa cells has recently provided evidence for some enzymatic deficits in steroidogenesis and altered response to gonadotrophins. Therefore, improving androgen environment of women classified in Poseidon Group 3 should be considered. In this clinical situation, the potential benefit of androgen supplementation or stimulation of theca cells by LH-activity products are respectively discussed.

The Impact of Embryo Quality on Pregnancy Outcomes in Single Day 5 versus Day 6 Euploid Blastocyst Transfer: A Retrospective Cohort Study.

BACKGROUND: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation. MATERIALS AND METHODS: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022. RESULTS: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality. CONCLUSION: The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.

Management of Etonogestrel implant migration into the pulmonary artery.

OBJECTIVES: To evaluate the relationship between time since contraceptive implant placement and retrieval outcomes in patients with implant migration into the pulmonary artery. STUDY DESIGN: We reviewed all cases of pulmonary artery implant migration referred to the Marie Lannelongue hospital from 2015 through 2020. Using our hospital database, we collected patients' clinical data and removal information to assess the success of therapeutic management according to the delay between implant insertion and removal. RESULTS: We identified 8 cases. Physicians located 2 in the upper and 6 in the lower lobe. Five patients had associated pulmonary symptoms, most commonly, chest pain and dyspnea. Physicians attempted an endovascular procedure in all cases with successful removal in 3 patients. In the 5 failures, angiography displayed arterial thrombosis distal to the implant. These patients had successful removal with an open mini-thoracotomy (< 5 cm). None of the 8 patients had serious post-operative complications. For the 3 patients with successful endovascular retrieval, 2 had early diagnosis (≤ 3 months). CONCLUSION: Endovascular approach with angiography should be performed as a first line treatment modality. Endothelialization and fibrosis within the vessel represent the principal limitations of endovascular strategy, but a retrieval could be attempted anyway with caution. In case of failure, an open approach is required. IMPLICATIONS STATEMENT: When a migration into the pulmonary artery is diagnosed, health care professionals should refer patients as soon as possible to a tertiary center with a vascular surgery and/or interventional radiology and thoracic surgery departments.

Conventional ovarian stimulation no longer exists: welcome to the age of individualized ovarian stimulation.

The prediction of extremes of ovarian response to stimulation and the irreversibility of reduced ovarian reserve remain important clinical and basic science research issues of IVF treatment. Recommending commencement of ovarian stimulation using any of the available exogenous compounds without knowledge of individual ovarian potentials is simplistic and dangerous because of the possible adverse consequences for the woman. The identification of groups of patients likely to benefit from one protocol than another is central to the workup process of IVF. Determining the agents for ovarian stimulation as well as the combination of them, the daily dose and duration according to some background information should be seen as the way to enhance safety and cost-effectiveness. This discussion paper aims to introduce the concept of individualized ovarian stimulation in routine clinical practice and to generate interest for tailored stimulation protocols.

Assessment of theca cell function prior to controlled ovarian stimulation: the predictive value of serum basal/stimulated steroid levels.

BACKGROUND: Serum androgen levels correlate with ovarian sensitivity to follicle-stimulating hormone (FSH) but in practice, standard baseline serum testosterone (T) levels prior to in-vitro fertilization (IVF) may not be the most appropriate marker for determination. METHODS: Infertile women enrolled in an IVF programme were included in this study. Serum T and Delta4-androstenedione (A), and the androgen precursor 17-hydroxyprogesterone (17-OHP) were measured before and 24 h after a gonadotrophin-releasing hormone agonist stimulation test (GAST). An early follicular phase antral follicle count (AFC) was also performed. Patients were subsequently enrolled in a long gonadotrophin-releasing hormone agonist protocol with a standard FSH dose (150 IU) for 7 days to assess the association between androgen levels and ovarian responsiveness to FSH. RESULTS: The GAST elicited a significant increase in serum androgen levels that was well correlated with AFC. 17-OHP showed the greatest response to GAST and strongest correlation with AFC. The 17-OHP response to GAST differentiated patients with high ovarian reserve (OR) from those with low or normal OR as assessed by AFC, whereas only the estradiol response could differentiate those with low AFC. GAST-stimulated serum levels of 17-OHP were also correlated with ovarian response to FSH. Using receiver operating characteristic curve analysis, stimulated 17-OHP levels were predictive of the ovarian response to controlled ovarian stimulation, with similar power to that observed with AFC but lower power than with anti-Müllerian hormone. CONCLUSIONS: Serum androgen levels following GAST are correlated with AFC and ovarian response to FSH. Serum T is a less sensitive marker of theca cell function than 17-OHP.

Comparative Effectiveness of Mild or Conventional GnRH-Antagonist Protocols for Ovarian Stimulation in Poor Responders (Poseidon Group 4).

Background and Aims: A panel of experts (the Poseidon Group) introduced a new and more detailed stratification for poor ovarian responders in order to predict the prognosis of IVF outcome according to the sensitivity to FSH. However, various arguments about the management strategy of these patients still remain, including the convenience and the cost. Therefore, this study was conducted to compare the efficacy of mild and conventional GnRH antagonist ovarian stimulation prescribed in patients classified in Poseidon Group 4. Methods: This retrospective cohort study included 359 poor responder patients (Poseidon Group 4) treated with mild or conventional GnRH antagonist stimulation regimens from 8/2017 to 7/2019 at Tam Anh Hospital ART Center. The main outcomes were the index of Follicular Output Rate (FORT) or Follicle to Oocyte Index (FOI), the number of day-2 embryos and top-quality embryos obtained. The t-test and Mann-Whitney U test in SPSS v25.0 was used to analyze the continuous data and Chi-squared/Exact test was used for binary variables. Multiple linear regression analysis was done by using Stata versions 15.0 to measure association between primary endpoints with stimulation regimen controlled for covariates and possible confounding factors. Results: In the overall group of poor responders, the conventional GnRH antagonist protocol performed better than the mild protocol. Subsequently, data were analyzed according to the AFC. In women with AFC < 3, no significant differences were observed between the 2 regimens regarding FORT (p = 0.71), FOI (p = 0.12), the number of day-2-embryos (p = 0.052) and the number of top-quality embryos (p = 0.26). In contrast, in women with AFC ≥ 3, mild stimulation regimen resulted in significantly poorer outcome compared to the conventional GnRH antagonist regimen, regarding FORT (p < 0.01), FOI (p < 0.01), the number of day-2-embryos (p < 0.01) and top-quality embryos (p = 0.01). Conclusions: Considering poor responders classified in Poseidon Group 4, both ovarian stimulation regimens resulted in similar outcome for patients with a very low ovarian reserve (AFC < 3). In contrast, the GnRH conventional antagonist protocol with maximum initial FSH dose (300-375 IU/day) and supplementary LH (75-150 IU/day) was more effective than the mild one for patients whose ovarian reserve was less reduced. The Clinical Trial was approved by the Ethnical Biomedical Research Committee Tam Anh General Hospital.

[Impact of overweight on the outcome of ovarian stimulation]. / Influence de l'excès pondéral sur les approches d'induction de l'ovulation.

Overweight and obesity have a negative impact on the efficacy of agents used to induce ovulation, and especially on the dose of clomiphene citrate or gonadotrophins required to achieve ovulation. BMI is a major predictor of the ovarian response. In IVF-ICSI cycles, overweight is associated with a decrease in the number of oocytes. While the pregnancy rate is not dependent on weight, the risk of early miscarriage is increased in obese women. Therefore, overweight should be managed before ovarian stimulation begins. The efficacy of insulin-sensitizing agents such as metformin is not fully clear, but their combination with clomiphene citrate or FSH seems promising.

Second live birth after undergoing assisted reproductive technology in women operated on for endometriosis.

OBJECTIVE: To determine prognostic factors for a second live birth, after a first child obtained through assisted reproductive techniques (ART). DESIGN: Observational study from January 2004 to December 2014. SETTING: Tertiary care university hospital and ART center. PATIENT(S): A total of 164 infertile patients with endometriosis, who underwent laparoscopy surgery and had a first baby obtained by ART, were included and 65 wished a second baby. INTERVENTION(S): No iterative surgery. MAIN OUTCOME MEASURE(S): Spontaneous pregnancy rate (PR) according to endometriosis fertility index. RESULT(S): Among the cohort, 27 patients (41.5%) gave birth to a second child through spontaneous pregnancy, whereas 23 patients (35.3%) required ART to obtain a second live birth. No difference was observed between patients regarding age, endometriosis staging, complete removal of endometriosis lesions and pelvic adhesion, except for the least function score, and the endometriosis fertility index. Taking into account irrespective of both mode of conception a total of 78% of patients obtained a second child, with a median conception time of 17 months. CONCLUSION(S): The second live birth rate in infertile patients with endometriosis and with surgical treatment was high (78%). Spontaneous PR was 54%. Endometriosis fertility index could be considered as a predictive factor for a spontaneous second pregnancy in fertility management. Our results need to be confirmed in larger prospective studies.

External validation of the Endometriosis Fertility Index in a French population.

OBJECTIVE: To show an external validation of the Endometriosis Fertility Index (EFI) and to observe cumulated pregnancy rates after infertility management combining surgery and assisted reproductive technologies (ART). DESIGN: Observational study from January 2004 to December 2012. SETTING: Tertiary-care university hospital and ART center. PATIENT(S): Four hundred twelve infertile and endometriotic patients after laparoscopic surgery. INTERVENTION(S): Surgical diagnosis and treatment followed by spontaneous fertility or ART management. MAIN OUTCOME MEASURE(S): Spontaneous pregnancy rates and cumulative (spontaneous and ART) pregnancy rates according to the EFI. RESULT(S): A significant relationship between EFI and spontaneous pregnancy rates was observed at 12 months (P=.001). The least function score and complete removal of endometriotic lesions and pelvic adhesions were significantly associated with spontaneous pregnancy (P=.006). Cumulative pregnancy rate at 18 months was 78.8%. ART benefits for pregnancy rates were higher for patients with poor EFI. CONCLUSION(S): External validation of the EFI in a French population was demonstrated. Combining surgery for endometriosis and ART led to a 78.8% pregnancy rate at 18 months after surgery.

Comparison of the effectiveness of recombinant and urinary FSH preparations in the achievement of follicular selection in chronic anovulation.

In order to compare the effectiveness of urinary and recombinant FSH (rFSH) preparations in achieving the threshold of follicular growth, stimulated cycles from patients with chronic anovulation, treated with a constant dose of FSH until the emergence of a selected follicle, were retrospectively analysed. Sixty-four cycles were performed using a similar starting dose of either urinary FSH (group 1) or rFSH (group 2), which was kept constant up to the time of follicular selection, assessed on ultrasound (follicular diameter >10 mm). The results of this study showed that, while the number of selected follicles was similar, the mean daily FSH dose required to achieve the threshold of follicular selection was significantly lower in group 2 (70.4 +/- 3.4 IU/day) than in group 1 (86.5 +/- 4 IU/day; P < 0.005). Furthermore, at the time of human chorionic gonadotrophin (HCG) administration, the total FSH dose was significantly lower in group 2 than in group 1, but plasma oestradiol values were equivalent. These data suggest that the higher effectiveness of rFSH preparations over urinary ones may be explained by a lower threshold dose required to achieve follicular selection.

Comparative use of urinary and recombinant human chorionic gonadotropins in women.

Human chorionic gonadotropin (hCG) preparations have been widely used as a surrogate for the mid-cycle luteinizing hormone (LH) surge for several decades. The urinary source of hCG preparations was favored for many years because of the easy collection of the starting material. However, the final structure of these urinary-derived preparations appears to be quite different from the natural placenta product. Furthermore, many disadvantages of these commercial preparations have been reported, such as local adverse events and immunologic reactions. The recent advent of recombinant DNA technology has now made recombinant hCG (r-hCG) available. This new product ensures high purity and batch-to-batch consistency. The pharmacokinetic and pharmacodynamic profiles of both urinary and recombinant preparations are quite similar. In clinical practice, several trials have been performed to compare both the efficacy and safety of urinary hCG (u-hCG) and r-hCG preparations. Overall, the reported data show that r-hCG preparations are at least as effective as u-hCG products in reproducing the follicular events surrounding the endogenous LH surge. Moreover, the r-hCG products ensure a better hormonal environment during the luteal phase. Finally, the overall tolerability of r-hCG preparations has been shown to be much better than that of u-hCG preparations. As a consequence, the newly available r-hCG preparations offer the first opportunity for clinicians to treat anovulatory women with a full range of recombinant products.

Clinical predictive criteria associated with live birth following elective single embryo transfer.

OBJECTIVE: We aimed to define clinical criteria from the patients related to the occurrence of live birth in case of elective single embryo transfer (eSET). STUDY DESIGN: We analyzed retrospectively 409 eSET at day 2/3 between March 2005 and July 2012, proposed in case of (i) woman's age <37 years, (ii) first/second IVF0 cycle, (iii) ≥2 good quality embryos obtained (3-5/6-10 blastomeres at day 2/3 and <20% fragmentation), including one top embryo (4/8 cells). In all, 124/409 live births (30.3%) were obtained, separating patients into groups of women who had birth or not. Different clinical parameters of interest were compared between each group, using appropriate statistical tests at p<0.05 significance level. RESULTS: By comparing Body Mass Index (BMI), we report a statistically higher BMI among women who did not deliver (24.6 vs. 23.4kg/m(2); p=0.014). Using an analysis by BMI categories, we also precise a threshold of BMI≥30kg/m(2), negatively associated with the occurrence of live birth. CONCLUSION: BMI appears to be the only clinical parameter statistically associated with delivery following eSET strategy in a good prognosis infertile population.

Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

Could sperm grade under high magnification condition predict IMSI clinical outcome?

OBJECTIVE: The aim of this study was to examine whether injection of first-best morphology grade selected spermatozoa improves live birth rate (LBR) compared to intracytoplasmic morphologically selected sperm injection (IMSI) using second-best grade sperm. STUDY DESIGN: In this prospective observational study, 132 patients were enrolled. Inclusion criteria were the presence of severe male factor (normal spermatozoa <10% in fresh ejaculated semen and <10% in selected sperm according to David's classification) associated with ≤2 previous ICSI failure. Results of IMSI performed with either first- or second-best morphology grade spermatozoa (according to Vanderzwalmen's classification) were compared. IMSI attempts performed using mixed first- and second-best grade spermatozoa were excluded (n=41). The primary endpoint was LBR. RESULTS: LBR following IMSI was not statistically different using first- (33.3% (13/39)) or second-best morphology grade spermatozoa (28.9% (15/52)). Our study shows that sperm grading under high magnification using Vanderzwalmen's classification is not correlated to IMSI outcome. CONCLUSION: We do not validate Vanderzwalmen classification in our external and prospective series. These results point out the need for improving our knowledge about the impact of observed vacuoles under high magnification condition.

Assessment of theca cell function: a prerequisite to androgen or luteinizing hormone supplementation in poor responders.

Poor responders are a heterogeneous population, with some patients displaying a diminished ovarian reserve and others a poor ovarian reserve with preserved granulosa cell function. Androgen and LH/hCG supplementation has been advocated for poor responders, mainly those >40 years old. Although androgens synergistically act with FSH to support folliculogenesis, and ovarian androgen secretion declines with age, there is still no evidence that androgen therapy is actually effective to improve ovarian FSH sensitivity. The main reason seems to be that theca cell function has not been appropriately assessed in patients at risk of poor response. The definition of theca insufficiency is hampered by methodologic shortcomings in routine bioassays. Provocative tests for theca cells might help to identify those patients who could benefit from androgen supplementation. The lack of data regarding theca cells in these patients might contribute to explaining the absence of evidence for a positive effect of androgen therapy.

Is intracytoplasmic morphologically selected sperm injection effective in patients with infertility related to teratozoospermia or repeated implantation failure?

OBJECTIVE: To evaluate the potential benefit of intracytoplasmic morphologically selected sperm injection (IMSI) in patients selected for either severe teratozoospermia or repeated implantation failure after conventional intracytoplasmic sperm injection (ICSI). DESIGN: Prospective nonrandomized observational study. SETTING: University hospital assisted reproduction unit. PATIENT(S): Four hundred seventy-eight patients were enrolled to evaluate ICSI and IMSI results for two indications. The first group (T) was composed of patients with severe teratozoospermia (<10% normal spermatozoa in fresh ejaculated and selected semen, according to David classification) and no or one previous ICSI failure. In the second group (IF), patients with at least two previous failed ICSI attempts were enrolled in absence of severe male factor (>10% normal spermatozoa in fresh ejaculated semen and >20% in selected sperm). INTERVENTION(S): ICSI/IMSI, biologic, and clinical data collection. MAIN OUTCOME MEASURE(S): Live-birth rate (LBR). RESULT(S): In group T, LBR was significantly higher when IMSI procedure was used compared with ICSI (38% [50/132] vs. 20% [25/126]). However, LBR observed in group IF was not significantly different between IMSI and ICSI procedures (21% [19/90] vs. 22% [28/130]). CONCLUSION(S): IMSI procedure is a valuable option for patients with severe teratozoospermia at their first or second attempts, but it does not improve pregnancy rate in patients with repeated ICSI failures in the absence of severe male factor.

Pretreatment with estrogen does not affect IVF-ICSI cycle outcome compared with no pretreatment in GnRH antagonist protocol: a prospective randomized trial.

OBJECTIVE: To assess effects of estrogen pretreatment in GnRH antagonist protocol. DESIGN: Prospective, randomized multicenter study. SETTING: Ten private or university-based centers. PATIENT(S): A total of 472 patients undergoing IVF/ICSI. INTERVENTION(S): Randomization by sealed envelopes to receive 17ß-estradiol (4 mg/d) or no pretreatment before daily recombinant FSH administration started on the first day of estrogen discontinuation or on cycle day 2 in nonpretreated women. MAIN OUTCOME MEASURE(S): The primary outcome measure was the number of retrieved oocytes. Secondary efficacy variables included total FSH dose, cycle duration, and outcome. RESULT(S): The mean numbers of retrieved oocytes (10.9 ± 5.7 vs. 10.2 ± 5.6) and obtained embryos (5.5 ± 3.7 vs. 4.8 ± 3.7) were not significantly different between women allocated to estrogen pretreatment (n = 238) and no pretreatment (n = 234). Total FSH amount (1,557 ± 408 vs. 1,389 ± 347 IU) and stimulation duration (10.8 ± 1.4 vs. 10.0 ± 1.5 days) were slightly but significantly increased in pretreated patients. Positive pregnancy tests, ultrasound pregnancy rate, and delivery rate per cycle were similar (36%, 33%, and 26.6%, respectively, vs. 38.2%, 35.4%, and 30%). CONCLUSION(S): These data confirm that estrogen pretreatment is associated with requirement of higher FSH doses and longer duration of stimulation without any significant increase in the number of retrieved oocytes. However, estrogen does not affect cycle outcome and therefore might be used in clinical practice for programming IVF retrievals during working days. CLINICAL TRIALS REGISTRATION NUMBER: NCT01489852.