Cumulative live birth rate after ovarian stimulation with freeze-all in women with polycystic ovaries: does the polycystic ovary syndrome phenotype have an impact?

RESEARCH QUESTION: Do cumulative live birth rates (CLBR) differ between polycystic ovary syndrome (PCOS) phenotypes when a freeze-all strategy is used to prevent OHSS after ovarian stimulation? DESIGN: A single-centre, retrospective cohort study of 422 women with PCOS or polycystic ovarian morphology (PCOM), in whom a freeze-all strategy was applied after GnRH agonist triggering because of hyper-response in their first or second IVF/ICSI. Primary outcome was CLBR; multivariate logistic regression analysis was used. RESULTS: Phenotype A (hyperandrogenism + ovulation disorder + PCOM [HOP]) (n = 91/422 [21.6%]); phenotype C (hyperandrogenism + PCOM [HP]) (33/422 [7.8%]; phenotype D (ovulation disorder + PCOM [OP]) (n = 161/422 [38.2%]); and PCOM (n = 137/422 [32.5%]. Unadjusted CLBR was similar among the groups (69.2%, 69.7%, 79.5% and 67.9%, respectively; P = 0.11). According to multivariate logistic regression analysis, the phenotype did not affect CLBR (OR 0.72, CI 0.24 to 2.14 [phenotype C]; OR 1.55, CI 0.71 to 3.36 [phenotype D]; OR 0.84, CI 0.39 to 1.83 [PCOM]; P = 0.2, with phenotype A as reference). CONCLUSIONS: In women with PCOS, hyper-response after ovarian stimulation confers CLBR of around 70%, irrespective of phenotype, when a freeze-all strategy is used. This contrasts with unfavourable clinical outcomes in women with hyperandrogenism and women with PCOS who underwent mild ovarian stimulation targeting normal ovarian response and fresh embryo transfer. The results should be interpreted with caution because the study is retrospective and cannot be generalized to all cycles as they pertain to those in which hyper-response is observed.

Impact of endometrial polyps detected during the follicular phase of intrauterine insemination treatments.

RESEARCH QUESTION: Endometrial polyps are a frequent finding during fertility treatment. Although up to 27% of small polyps (<10 mm) regress spontaneously, there is clinical benefit to removing a polyp detected before intrauterine insemination (IUI), regardless of size. However, the clinical outcome of IUI following a new suspicion of a polyp during follicle tracking is unknown. DESIGN: This retrospective cohort study included all patients with a normal baseline uterine ultrasound and/or hysteroscopy result who started an IUI cycle between May 2009 and March 2017. In 139 of 6606 patients (2.1%), encompassing 340 out of 15,147 cycles (2.3% of cycles), a polyp was diagnosed during the follicular phase. The 6467 controls had ultrasound results with no suspicion of a polyp. Each patient was included only once in the analysis during a maximum of three consecutive cycles of IUI. RESULTS: Female age was significantly higher in the polyp group than the controls (35.4 ± 4.8 versus 33.0 ± 5.0, P < 0.01). The unadjusted cumulative live birth rate (CLBR) after three IUI cycles in women with and without a polyp was 24.1% versus 33.0% (P = 0.03), indicating a deleterious effect of polyp(s). However, after multivariate Cox regression analysis for body mass index, female age, number of follicles and sperm concentration, the presence of a polyp appeared not to influence the CLBR (adjusted hazard ratio 0.742, 95% confidence interval 0.477-1.156, P = 0.19). CONCLUSIONS: These results may be reassuring, as ultrasound diagnosis of a polyp during the follicular phase of an IUI cycle does not seem to compromise clinical outcome when previous baseline examinations have been normal.

Undetectable viral RNA in follicular fluid, cumulus cells, and endometrial tissue samples in SARS-CoV-2-positive women.

OBJECTIVE: To study the presence of viral RNA in the follicular fluid, cumulus cells, and endometrial tissue samples in SARS-CoV-2-positive women undergoing assisted reproductive technology (ART). DESIGN: Prospective, single-center, observational study. SETTING: Tertiary hospital. PATIENT(S): A total of 16 patients undergoing transvaginal oocyte retrieval who had a positive SARS-CoV-2 RNA test <48 hours before the procedure. All patients underwent the retrieval between September 2020 and June 2021 and used in vitro fertilization or intracytoplasmic sperm injection. All embryos were vitrified to avoid conception during SARS-CoV-2 infection. INTERVENTION(S): Follicular fluid aspirated during oocyte retrieval, cumulus cells, and endometrial samples were analyzed for SARS-CoV-2 RNA using the RealStar SARS-CoV-2 RT-PCR-Kit1.0. MAIN OUTCOME MEASURE(S): The primary outcome parameter was the detection of viral RNA in the follicular fluid, cumulus cells, and endometrial cells. Fertilization rate, embryo developmental potential, and clinical outcome after frozen embryo transfer were secondary outcome parameters. RESULT(S): Samples from 16 patients were analyzed. Cycle threshold values of <40 were considered positive. All samples were negative for SARS-CoV-2 viral RNA. No inflammatory lesions of the endometrium were identified histologically. Fertilization rate, embryo development, and clinical outcomes after embryo transfer were reassuring. CONCLUSION(S): In women infected with SARS-CoV-2 who underwent ART, viral RNA was undetectable in the follicular fluid, cumulus cells, and endometrium. Caution is warranted in view of the small sample size, and the risk of SARS-CoV-2 affecting the embryo via ART cannot be ruled out. Adequate counseling of women and couples undergoing ART is crucial in parallel with further research on the effect of exposure of the early human embryo to SARS-CoV-2. CLINICAL TRIAL REGISTRATION NUMBER: NCT04425317.

Type and dose of gonadotropins in poor ovarian responders: does it matter?

Infertile patients with a diminished ovarian reserve, also referred to as poor ovarian responders, constitute a substantial and increasing population of patients undergoing in vitro fertilization. The management of patients with poor ovarian response is still a controversial issue. Almost a century has passed since the introduction of the first gonadotropin. A broad collection of urinary and recombinant gonadotropins, including biosimilars, is commercially available now. Despite great advances in assisted reproductive technology, there remains uncertainty about the optimal treatment regimen for ovarian stimulation in poor ovarian responders. Although oocyte donation is the most successful and ultimate remedy for poor ovarian responders, most patients persist on using their own oocytes in several attempts, to achieve the desired pregnancy. The aim of this review is twofold: first, to provide an overview of the commercially available gonadotropins and summarize the available evidence supporting the use of one or another for ovarian stimulation in poor ovarian responders, and second, to address the controversies on the dosage of gonadotropins for this specific in vitro fertilization population.

Update on the management of poor ovarian response in IVF: the shift from Bologna criteria to the Poseidon concept.

Despite the considerate progress to which assisted reproduction technology (ART) has been subject since 1978, some issues remain unresolved. Notably, the clinical management of patients with a poor ovarian response is still a challenge in everyday practice, frustrating to both the patient and the fertility expert. Poor ovarian responders (PORs) embody 9-24% of patients undergoing ovarian stimulation, meaning that up to one in four patients conceals a poor reproductive prognosis. The last decade has witnessed the attempts of the medical community to standardize diagnosis of POR with the developing of the Bologna Criteria and the subsequent evolution of the low prognosis patient elaborated in the POSEIDON classification. The aim of this article is to summarize all evidence concerning etiology and management of poor ovarian response, including the most recent advances and future prospects in this regard.