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STUDY QUESTION Does late follicular-phase elevated serum progesterone (LFEP) during ovarian stimulation for oocyte donation have an impact on embryo quality (EQ) and cumulative live birth rate (CLBR)? SUMMARY ANSWER LFEP does not have an influence on EQ nor CLBR in oocyte donation cycles. WHAT IS KNOWN ALREADY Ovarian stimulation promotes the production of progesterone (P) which, when elevated during the follicular phase, has been demonstrated to have a deleterious effect in autologous fresh IVF outcomes. While there is robust evidence that this elevation results in impaired endometrial receptivity, the impact on EQ remains a matter of debate. The oocyte donation model is an excellent tool to assess the effects of LFEP on EQ from those on endometrium receptivity separately. Previous studies in oocyte donation cycles investigating the influence of elevated P on pregnancy outcomes in oocyte recipients showed conflicting results. STUDY DESIGN, SIZE, DURATION This is a retrospective analysis including all GnRH antagonist down-regulated cycles for fresh oocyte donation taking place in a tertiary referral university hospital between 2010 and 2017. A total of 397 fresh donor-recipient cycles were included. Each donor was included only once in the analysis and could be associated to a single recipient. PARTICIPANTS/MATERIALS, SETTING, METHODS The sample was stratified according to serum P levels of ≤1.5 and >1.5 ng/mL on the day of ovulation triggering. The primary endpoint of the study was the top-quality embryo rate on Day 3, and the secondary outcome measure was CLBR defined as a live-born delivery beyond 24 weeks. MAIN RESULTS AND THE ROLE OF CHANCE Three hundred ninety-seven fresh oocyte donation cycles were included in the analysis, of which 314 (79%) had a serum P ≤ 1.5 ng/mL and 83 (20.9%) had a serum P > 1.5 ng/mL. The average age of the oocyte donors was 31.4 ± 4.7 and 29.9 ± 4.5 years, respectively, for normal and elevated P (P = 0.017). The mean number of oocytes retrieved was significantly higher in the elevated P group with 16.6 ± 10.6 vs 11.5 ± 6.9 in the P ≤ 1.5 group (P < 0.001). In parallel, the total number of embryos on Day 3, as well as the number of good-quality embryos at this stage, was significantly higher in the elevated P group (6.6 ± 5.6 vs 4.15 ± 3.5 and 8.7 ± 6.3 vs 6.1 ± 4.4; respectively, P < 0.001). However, maturation and fertilization rates did not vary significantly between the two study groups and neither did the top- and good-quality embryo rate and the embryo utilization rate, all evaluated on Day 3 (P = 0.384, P = 0.405 and P = 0.645, respectively). A multivariable regression analysis accounting for P groups, age of the donor, number of retrieved oocytes and top-quality embryo rate as potential confounders showed that LFEP negatively influenced neither the top-quality embryo rate nor the CLBR. LIMITATIONS, REASONS FOR CAUTION This is an observational study based on a retrospective data analysis. Better extrapolation of the results could be validated by performing a prospective trial. Furthermore, this study was focused on oocyte donation cycles and hence the results cannot be generalized to the entire infertile population. WIDER IMPLICATIONS OF THE FINDINGS This is the first study providing evidence that LFEP does not influence CLBR and is adding strong evidence to the existing literature that LFEP does not harm EQ in oocyte donation programs. STUDY FUNDING/COMPETING INTERESTS Not applicable.

Research Question: Does reproductive outcome differ among the various subgroups of poor ovarian responders according to the Bologna criteria?Design: This was a retrospective, cohort study including poor ovarian responders according to Bologna criteria, undergoing an ICSI cycle from January 2011 until December 2017. Patients were divided into four groups: (1) age ≥ 40 years and abnormal ovarian response test, (2) age ≥ 40 years, abnormal ovarian reserve test and one previous poor response to stimulation, (3) age ≥ 40 years and one previous poor response, (4) abnormal ovarian reserve test and one previous poor response.Result(s): Overall, 846 cycles in 706 Bologna poor ovarian responders were included: 310 cycles in group 1, 169 in group 2, 52 in group 3, and 315 in group 4. There were significant differences in age, antral follicle count, antimüllerian hormone, cycle cancellation rates, and number of retrieved oocytes between the four groups. Live birth and cumulative live birth rate differed significantly between groups and were highest in Group 4 [Live birth rate: 7.4% (1) vs. 4.1% (2) vs. 5.8% (3) vs. 13.4% (4), p = 0.001 and Cumulative live birth rate: 8.3% (1) vs. 4.1 % (2) vs. 9.6% (3) vs. 16.8% (4) p < 0.001]. The multivariate GEE analysis revealed that the number of MIIs and the Bologna criteria pattern were the variables which were significantly associated with cumulative live birth rate. Conclusion(s):Poor ovarian responders represent a heterogeneous population. The young subpopulation has a better clinical prognosis in terms of fresh and cumulative live birth rate.

Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly purified human menopausal gonadotrophin (hp-hMG). Objective: To compare cumulative LBRs in Bologna poor ovarian responders undergoing ovarian stimulation with CFA followed by hp-hMG vs. hp-hMG alone in a GnRH antagonist protocol. Design: This is a retrospective cohort study. We included in total 917 poor responders fulfilling the Bologna criteria for poor ovarian response (POR) at a university-affiliated tertiary center from January 2011 until March 2017. Patients were administered either fixed daily doses of 300–450 IU of hp-hMG (group A) or a single dose of 150 μg of CFA followed by daily injections of ≥300 IU of hp-hMG from Day 8 of stimulation until the day of ovulation trigger (group B), in a fixed GnRH antagonist protocol. Results: LBRs after fresh embryo transfer (ET) were similar in group A 71/510 (14%) and B 42/407 (10%). Cumulative LBR per cycle was significantly higher in group A (16.9%) compared to group B (11.8%); ( P = 0.03). However, logistic regression analysis showed no association between the type of gonadotropin administered and cumulative LBR. Only age was significantly associated with cumulative LBR (OR = 0.93, P = 0.007). Conclusion: Cumulative LBRs are similar in Bologna poor responders stimulated with CFA followed by hp-hMG compared to hp-hMG monotreatment in an antagonist protocol.

He is currently training at CRG, UZ Brussel, and his clinical and research interests are ovarian stimulation and reproductive endocrinology.

A 40-year-old nulliparous woman with no medical history attended our fertility center with the desire to become pregnant with sperm donation. Her ovarian reserve was moderately low (Anti-Müllerian hormone, 0.9 ng/mL; antral follicle count, 7) and she was advised to start in-vitro fertilization/intracytoplasmic sperm injection (ICSI) treatment. Two cleavage-stage embryos were transferred 3 days following oocyte retrieval. Twelve days later, serum beta-human chorionic gonadotropin (β-hCG) was positive.The first transvaginal ultrasound (TVS) scan at 7 weeks revealed an ectopic twin pregnancy, with one embryo in each cornu, both with cardiac activity. The gestational sacs (GS) were 11.6 mm and 18.5 mm in diameter ( Figure 1). Following a second TVS examination, the patient was administered a first intramuscular injection of 75 mg methotrexate (MTX) at 8 weeks, however, a second dose was indicated, as there was no decrease in β-hCG after 7 days. One week later, TVS showed evolution and viability of the right pregnancy, so it was decided to perform a TVS-guided reduction of the pregnancy. The left cornual pregnancy without viability was injected with 100 mg/mL MTX, whereas the right cornual pregnancy received an intracardiac injection of 3 mEq potassium chloride (KCl) and 150 mg/1.5 mL of MTX intragestationally, using a Towako needle set (Cook Medical, Bloomington, IN, USA). TVS performed 1 week later showed an empty and collapsed sac in the right cornu ( Figure 2). After 3 weeks, serum β-hCG was negative. A new treatment cycle with ICSI was started, which resulted in a biochemical pregnancy. In the next cycle, a thawed embryo was transferred and the patient had an ongoing eutopic pregnancy when she was last examined at 7 weeks' gestation.Cornual pregnancy occurs in 2-4% of all ectopic pregnancies, with a mortality rate of 2-3% 1 . Some studies report higher ectopic pregnancy rates after assisted reproductive technology (ART) cycles 2 , whereas others report similar ectopic implantation rates between spontaneous and assisted conception 3 . One factor contributing to ectopic pregnancy following ART cycles related to embryo implantation potential 3 . Another Figure 1 Three-dimensional ultrasound imaging of uterine fundus with gestational sacs in both cornua in transverse (a) and coronal (b) views, showing distention of the cornua and thin residual myometrium (a) and different implantation sites in each cornu (b).