BackgroundThe association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug.MethodsEight hundred forty-eight (848) IVF patients classified as expected “poor” or “normal” responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1–2, 3–4, 5–6, 7–8, >8).ResultsOverall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients’ characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively.ConclusionsWhen comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.

Purpose Does controlled ovarian stimulation (COS) and progesterone (P) luteal supplementation modify the vaginal and endometrial microbiota of women undergoing in vitro fertilization? Methods Fifteen women underwent microbiota analysis at two time points: during a mock transfer performed in the luteal phase of the cycle preceding COS, and at the time of fresh embryo transfer (ET). A vaginal swab and the distal extremity of the ET catheter tip were analyzed using next-generation 16SrRNA gene sequencing. Heterogeneity of the bacterial microbiota was assessed according to both the Bray-Curtis similarity index and the Shannon diversity index. Results Lactobacillus was the most prevalent genus in the vaginal samples, although its relative proportion was reduced by COS plus P supplementation (71.5 ± 40.6% vs. 61.1 ± 44.2%). In the vagina, an increase in pathogenic species was observed, involving Prevotella (3.5 ± 8.9% vs. 12.0 ± 19.4%), and Escherichia coli-Shigella spp. (1.4 ± 5.6% vs. 2.0 ± 7.8%). In the endometrium, the proportion of Lactobacilli slightly decreased (27.4 ± 34.5% vs. 25.0 ± 29.9%); differently, both Prevotella and Atopobium increased (3.4 ± 9.5% vs. 4.7 ± 7.4% and 0.7 ± 1.5% vs. 5.8 ± 12.0%). In both sites, biodiversity was greater after COS (p < 0.05), particularly in the endometrial microbiota, as confirmed by Bray-Curtis analysis of the phylogenetic distance among bacteria genera. Bray-Curtis analysis confirmed significant differences also for the paired endometrium-vagina samples at each time point. Conclusions Our findings suggest that COS and P supplementation significantly change the composition of vaginal and endometrial microbiota. The greater instability could affect both endometrial receptivity and placentation. If our findings are confirmed, they may provide a further reason to encourage the freeze-all strategy.

Purpose The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-müllerian hormone (AMH) and to investigate factors affecting their probability of pregnancy. Methods The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5 ng/ml was retrospectively analyzed. Results Cycle cancellation rate was 14.5 %; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35 years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35-39 or 40-43 (31 % vs. 23.2 % vs. 10.2 %, respectively; p = 0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14-0.49 ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level. Conclusions Women with very low (<0.5 ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF.

In this review, the definition, incidence and possible causes of empty follicle syndrome (EFS), including molecular mechanisms that may underlie the syndrome, are discussed, along with prevention and treatment options. EFS is the complete failure to retrieve oocytes after ovarian stimulation, despite apparently normal follicle development and adequate follicular steroidogenesis. Two variants of EFS have been described: the 'genuine' form (gEFS), which occurs in the presence of adequate circulating HCG levels at the time of oocyte aspiration, and the 'false' form (f-EFS), which is associated with circulating HCG below a critical threshold. Heterogeneous HCG concentration thresholds, however, have been used to define gEFS, and to date no standardization exist. The situation is unclear when GnRH-analogues are used for ovulation trigger, as the threshold circulating LH and progesterone levels used to define EFS as 'genuine' are not established. The cause of fEFS has been clearly identified as an error in HCG administration at the time of ovulation trigger; in contrast, the cause of gEFS is still unclear, although some pathogenetic hypotheses have been proposed. Optimal treatment and prognosis of these patients are still poorly understood. Large, systematic multi-centre studies are needed to increase the understanding of EFS.

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