[Impact of donor parity on oocyte donation outcomes]. / Impact de la parité des donneuses sur les résultats du don d'ovocytes.

OBJECTIVES: Since 2015, in France, men and women who have never procreated are allowed to donate their gametes. This has led to an increase in the number of female oocyte donors, whereas there are many couples waiting for gametes that have a long waiting time. The aim of this study is to compare the results of donation with oocytes from nulliparous and non-nulliparous donors. METHODS: Monocentric retrospective observational study (Lille University Hospital) between January 1st, 2016 and December 31st, 2019. Phenotypic characteristics and clinical and biological outcomes of oocytes donations were compared according to donor parity (nulliparous versus primiparous or multiparous). RESULTS: One hundred and eighty-five donors (66 nulliparous and 119 non-nulliparous) were included in the study, allowing 284 ICSI cycles to be performed in recipient couples. On average, 11.5 oocytes were obtained per donation cycle, of which 7.8 were mature. In total, 4.6 mature oocytes were obtained per attempt and per recipient couple. Nulliparous donors are younger than non-nulliparous ones. An early pregnancy was obtained in 55.6% of the nulliparous donors and in 50.8% of the non-nulliparous donors (P=0.55). A progressive pregnancy was obtained in 49.2% of the nulliparous women and in 42.1% of the non-nulliparous women (P=0.36). There was therefore no difference in terms of early pregnancy and ongoing pregnancy whether the donation came from a nulliparous or non-nulliparous woman. CONCLUSION: Donor parity does not seem to have an impact on the success of oocyte donation attempts.

A sharing oocyte donation program: a 15-year cohort stud.

OBJECTIVE: To evaluate clinical and laboratory outcomes of oocyte donation cycles and compare the results from donors and recipients. METHODS: A retrospective cohort study was conducted at a reproductive medicine center. A 586 first fresh oocyte donation cycles, performed from 01/2002 to 12/2017 were included. The outcomes of 290 cycles from donors and 296 from recipients, resulting in 473 fresh embryo transfers, were analyzed. The oocyte division was equally made, whereas, at an odd amount, the donor always had a preference. The data were collected from an electronic database, and analyzed using Chi-square test, Fisher's exact test, Mann-Whitney U-test or Student t-test depending on the data distribution, and multivariate logistic regression, considering p<0.05. RESULTS: The main results comparing donor and recipient, were, respectively: fertilization rate (72.0±21.4 vs. 74.6±24.2, p<0.001), implantation rate (46.2% vs. 48.5%, p=0.67); clinical pregnancy rate (41.9% vs. 37.7%, p=0.39), live birth rates by transfer (33.3 vs. 37.7, p=0.54). CONCLUSIONS: Oocyte donation is often the way donors can access in vitro fertilization, and for recipients seems to be a good option for pregnancy. Demographic and clinical characteristics have a secondary role in oocyte donors under 35 years and patient without comorbidities under 50 years and were not associated with pregnancy outcomes, emphasizing the power of oocyte quality on the success of intracytoplasmic sperm injection treatment. An oocyte-sharing program that offers good and comparable results is fair and worth being encouraged.

Does paternal age affect the live birth rate in donor oocyte cycles? A systematic review and meta-analysis.

PURPOSE: While delayed parenthood is increasing worldwide, the effect of paternal age on in vitro fertilization (IVF) outcomes remains unclear. The egg donation model appears to be relevant to studying the independent impact of paternal age on clinical outcome, but the available studies are heterogeneous and contradictory. This systematic review and meta-analysis aimed to assess the relationship between paternal age and live birth rate (LBR) in egg donation cycles. METHODS: A systematic search of the literature was conducted in PubMed, Embase, and the Cochrane Library from inception to June 30, 2021. All studies on egg donation cycles where LBR is reported according to male age were included. Study selection, bias assessment, and data extraction were performed by two independent reviewers according to the Cochrane methods. RESULTS: Eleven studies involving 10,527 egg donation cycles were finally included. The meta-analysis showed a slight but significant and linear decrease in LBR with increasing paternal age (estimate - 0.0055; 95% CI (- 0.0093; - 0.0016), p = 0.006), with low heterogeneity (I2 = 25%). No specific threshold was identified. A similar trend toward decreased clinical pregnancy rate with advancing paternal age was found but did not reach statistical significance (p = 0.07). CONCLUSION: This meta-analysis demonstrates that increasing paternal age is associated with a slight but significant and linear decrease in the live birth rate in egg donation cycles, with no apparent threshold effect. Although this requires further confirmation, this information is important for counseling men who are considering delayed childbearing.

Agonist triggering in oocyte donation programs-Mini review.

Oocyte donation programs involve young and healthy women undergoing heavy ovarian stimulation protocols in order to yield good-quality oocytes for their respective recipient couples. These stimulation cycles were for many years beset by a serious and potentially lethal complication known as ovarian hyperstimulation syndrome (OHSS). The use of the short antagonist protocol not only is patient-friendly but also has halved the need for hospitalization due to OHSS sequelae. Moreover, the replacement of beta-human chorionic gonadotropin (b-hCG) with gonadotropin-releasing hormone agonist (GnRH-a) triggering has reduced OHSS occurrence significantly, almost eliminating its moderate to severe presentations. Despite differences in the dosage and type of GnRH-a used across different studies, a comparable number of mature oocytes retrieved, fertilization, blastulation, and pregnancy rates in egg recipients are seen when compared to hCG-triggered cycles. Nowadays, GnRH-a tend to be the triggering agents of choice in oocyte donation cycles, as they are effective and safe and reduce OHSS incidence. However, as GnRH-a triggering does not eliminate OHSS altogether, caution should be practiced in order to avoid unnecessary lengthy and heavy ovarian stimulation that could potentially compromise both the donor's wellbeing and the treatment's efficacy.

Is It Possible to Expand Oocyte Donors by Decreasing Number of Oocytes for Own Use? Insights From a Large Single-Center Study.

Background: Currently, in China, only women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles can donate oocytes to others, but at least 15 oocytes must be kept for their own treatment. Thus, the aim of this study was to determine whether oocyte donation compromises the cumulative live birth rate (CLBR) of donors and whether it is possible to expand oocyte donors' crowd. Methods: This was a retrospective cohort study from August 2015 to July 2017 including a total of 2,144 patients, in which 830 IVF-embryo transfer (IVF-ET) patients were eligible for oocyte donation and 1,314 patients met all other oocyte donation criteria but had fewer oocytes retrieved (10-17 oocytes). All 830 patients were advised to donate approximately three to five oocytes to others and were eventually divided into two groups: the oocyte donation group (those who donated) and the control group (those who declined). The basic patient parameters and CLBR, as well as the number of supernumerary embryos after achieving live birth, were compared. These two factors were also compared in all patients (2,144) with oocyte ≥10. Results: In 830 IVF-ET patients who were eligible for oocyte donation, only the oocyte number was significantly different between two groups, and the donation group had more than the control group (25.49 ± 5.76 vs. 22.88 ± 5.11, respectively; p = 0.09). No significant differences were found between the two groups in other factors. The results indicate that the live birth rate in the donation group was higher than that in the control group (81.31% vs. 82.95%, p = 0.371), without significance. In addition, CLBR can still reach as high as 73% when the oocyte number for own use was 10. Supernumerary embryos also increased as the oocyte number increased in all patients (oocyte ≥10). Conclusions: Currently, oocyte donation did not compromise CLBR, and oocyte donation can decrease the waste of embryos. In addition, in patients with 10 oocytes retrieved, the CLBR was still good (73%). Thus, it is possible to expand oocyte donors if the number of oocyte kept for own use was decreased from 15 to 10 after enough communication with patients.

Preimplantation genetic testing for aneuploidies does not increase success rates in fresh oocyte donation cycles: a paired cohort study.

PURPOSE: To determine whether in vitro fertilization cycles using fresh oocyte donations benefit from preimplantation genetic testing for aneuploidies. METHODS: A paired cohort study compared 44 fresh oocyte donation cycles with or without preimplantation genetic testing for aneuploidy (PGT-A). The sibling oocyte study analyzed fertilized oocytes, blastocyst development, and euploidy rate. Only frozen embryo transfers were performed. Pregnancy, implantation, biochemical pregnancy, miscarriage, stillbirth, live birth, and twin pregnancy rates were analyzed between groups. RESULTS: Fresh oocyte donation cycles between PGT-A and non-PGT-A groups were similar in all laboratory and clinical outcomes. A euploidy rate of 74.2% was observed in the PGT-A group. Although a slight trend was observed for implantation rate in the PGT-A group, it was not statistically significant. No difference was observed for live birth between groups. CONCLUSION: PGT-A associated with fresh oocyte donation cycles does not improve clinical outcomes and can be seen as over-treatment for patients.

Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC). METHODS: We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups. RESULTS: Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively). CONCLUSIONS: Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

Day 5 vitrified blastocyst transfer versus day 6 vitrified blastocyst transfer in oocyte donation program.

The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, possibly due to heterogeneous patient population and embryo quality. The aim of this study was to compare clinical pregnancy rate (CPR) and live birth rate (LBR) between transfers of vitrified day 5 blastocysts and day 6 blastocysts in oocyte donation, blastocyst-only cycles. In a retrospective, multi-center study, with a single oocyte donation program, a total of 1840 frozen embryo transfers (FET's) were analyzed, including 1180 day 5 blastocysts and 660 day 6 blastocysts transfers. Day 5 blastocyst transfers had better embryonic development and significantly higher CPRs (34.24% vs. 20.15%, P < 0.0001), higher LBRs (26.89% vs. 14.77%, P < 0.0001), less cycles to LBR (1.83 ± 0.08 vs. 2.39 ± 0.18, P = 0.003) and shorter time to LBRs (76.32 ± 8.7 vs. 123.24 ± 19.1 days, P = 0.01), compared to day 6 transfers, respectively. A multivariate stepwise logistic regression indicated, that day 5 transfer was an independent factor for CPRs (OR 1.91; 95% CI 1.43-2.54, P < 0.001) and LBRs (OR 2.26; 95% CI 1.19-4.28, P = 0.01), regardless of embryo quality, compared to day 6. In conclusion, day 5 blastocysts in oocyte donation program have significantly higher CPRs and LBRs, and present shorter time to delivery, compared to day 6 blastocysts, regardless of embryo quality.

Differential sperm proteomic profiles according to pregnancy achievement in intracytoplasmic sperm injection cycles: a pilot study.

PURPOSE: To describe the proteomic profiles in semen samples and define the differences in sperm proteomic profiles among samples that ultimately achieved pregnancy (P) via intracytoplasmic sperm injection (ICSI) in an oocyte donation program and those that were unsuccessful (NP). METHODS: Prospective, analytical, observational nested case and control study evaluating the proteomic profile of spermatozoa from patients' ejaculates where pregnancies were (group pregnant (P), n= 4) or were not (group non-pregnant (NP), n=4) achieved after ICSI in an oocyte donation program aiming to standardize female factor. Proteins were separated and analyzed by means of SWATH-MS) and compared between P/NP groups to identify sperm biomarkers of fertility/infertility. Proteins are available via ProteomeXchange. RESULTS: We identified and quantified 2228 proteins, with 37 significantly higher in the P group and 16 higher in NP. Enrichment analysis revealed that the increased proteins in P group sperm were related to motility, anaerobic metabolism, and protein biosynthesis functions, while the increased proteins in the NP group were involved in protein biosynthesis, protein folding, aerobic metabolism, and signal transduction, all of which are functions not previously described as influencing sperm success. Some proteins identified (e.g., SLC2A3, or CD81) are located in the cell membrane and thus may be employed to select spermatozoa by magnetic-activated cell sorting (MACS). CONCLUSION(S): This work revealed differences in the proteomic profiles of sperm samples successful in achieving pregnancy and those that were not, expanding our understanding of sperm function and infertility-related molecular markers, and enabling the future development of male fertility diagnostic tools and therapies.

Medroxyprogesterone acetate is a useful alternative to a gonadotropin-releasing hormone antagonist in oocyte donation: a randomized, controlled trial.

OBJECTIVE: To compare ovarian response and reproductive outcomes in oocyte donors undergoing pituitary suppression with medroxyprogesterone acetate (MPA) versus those undergoing conventional treatment with a gonadotropin-releasing hormone (GnRH) antagonist. DESIGN: A prospective, randomized, controlled trial of cycles was conducted from October 2017 to June 2019 to evaluate ovarian response in terms of the number of oocytes. The reproductive outcomes of the recipients were retrospectively analyzed later. SETTING: A university-affiliated private in vitro fertilization center. PATIENT(S): We randomly divided 318 donors into 2 groups in a 1:1 ratio. The oocytes obtained were assigned to 364 recipients. One hundred sixty-one donors were treated with a daily dose of 10 mg of MPA administered orally from the beginning of ovarian stimulation (OS), and 156 were treated with a GnRH antagonist (initiated once the leading follicle reached a diameter of 13 mm). Transvaginal ultrasound was performed, and serum estradiol, luteinizing hormone, and progesterone levels were recorded during monitoring. The following additional parameters were analyzed: endocrine profile (in follicular fluid), number of metaphase II oocytes, and pregnancy outcome. INTERVENTION(S): The donors included in the study group were stimulated using recombinant follicle-stimulating hormone and MPA at 10 mg/day, simultaneously begun on cycle day 2 or 3. Ovulation was induced using a GnRH agonist when dominant follicles matured. A short protocol with ganirelix at 0.25 mg/day was used for the control group. Oocytes were assigned to the recipients, followed by routine in vitro fertilization procedures in which 1 embryo was usually transferred. MAIN OUTCOME MEASURE(S): The primary outcome measure was the numbers of oocytes and metaphase II oocytes retrieved. The secondary outcomes were the incidence of premature luteinizing hormone surge, serum and follicular fluid hormone profiles, and clinical pregnancy outcomes in the recipient group. RESULT(S): The number of oocytes retrieved was 21.4 ± 11.7 in the MPA group and 21.2 ± 9.2 in the antagonist group (mean difference 0.14; 95% confidence interval -2.233, 2.517). The total dose of recombinant follicle-stimulating hormone, duration of OS, and endocrine profiles of the serum and follicular fluids were comparable in the 2 groups. No early ovulation was observed in either group. No statistically significant differences with respect to implantation rate (68.1% in the MPA group vs. 62% in the antagonist group), clinical pregnancy rate (64.5% in the MPA group vs. 57.8 in the antagonist group), ongoing pregnancy rate (55.4% in the MPA group vs. 48.5% in the antagonist group), live birth rate (55.1% in the MPA group vs. 48.5% in the antagonist group), or cumulative live birth rate (73.8% in the MPA group vs. 70.7% in the antagonist group) were observed between the groups. CONCLUSION(S): The administration of MPA resulted in oocyte retrieval rates, endocrine profiles, viable embryo numbers, and pregnancy outcomes similar to those achieved with the GnRH antagonist. Therefore, MPA can be recommended for OS in oocyte donation because it permits a more patient-friendly approach. CLINICAL TRIAL REGISTRATION NUMBER: NCT03300960.

Ovarian stimulation for oocyte donation: a systematic review and meta-analysis.

BACKGROUND: Since its introduction in the 1980s, oocyte donation (OD) has been largely integrated into ART. Lately, both demand and the indications for OD have increased greatly. Oocyte donors are healthy and potentially fertile women undergoing voluntarily ovarian stimulation (OS). Selection of the optimal type of stimulation is of paramount importance in order to achieve the most favourable outcomes for the oocyte recipients, but most importantly for the safety of the oocyte donors. OBJECTIVE AND RATIONALE: This is the first systematic review (SR) with the objective to summarize the current evidence on OS in oocyte donors. The scope of this SR was to evaluate the OD programme by assessing four different aspects: how to assess the ovarian response prior to stimulation; how to plan the OS (gonadotrophins; LH suppression; ovulation trigger; when to start OS); how to control for the risk of ovarian hyperstimulation syndrome (OHSS) and other complications; and the differences between the use of fresh versus vitrified donated oocytes. SEARCH METHODS: A systematic literature search was conducted in May 2020, according to PRISMA guidelines in the databases PubMed and Embase, using a string that combined synonyms for oocytes, donation, banking, freezing, complications and reproductive outcomes. Studies reporting on the safety and/or efficacy of OS in oocyte donors were identified. The quality of the included studies was assessed using ROBINS-I and ROB2. Meta-analysis was performed where appropriate. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for binary data with their corresponding 95% CIs. Heterogeneity between the included studies was assessed using I2 and tau statistics. OUTCOMES: In total, 57 manuscripts were selected for the review, out of 191 citations identified. Antral follicle count and anti-Müllerian hormone levels correlate with ovarian response to OS in OD but have limited value to discriminate donors who are likely to show either impaired or excessive response. Five randomized controlled trials compared different type of gonadotrophins as part of OS in oocyte donors; owing to high heterogeneity, meta-analysis was precluded. When comparing different types of LH control, namely GnRH antagonist versus agonist, the studies showed no differences in ovarian response. Use of progesterone primed ovarian stimulation protocols has been evaluated in seven studies: the evidence has shown little or no difference, compared to GnRH antagonist protocols, in mean number of retrieved oocytes (MD 0.23, [95% CI 0.58-1.05], n = 2147; 6 studies; I2 = 13%, P = 0.33) and in clinical pregnancy rates among recipients (OR 0.87 [95% CI 0.60-1.26], n = 2260, I2 = 72%, P < 0.01). There is insufficient evidence on long-term safety for babies born. GnRH agonist triggering is the gold standard and should be used in all oocyte donors, given the excellent oocyte retrieval rates, the practical elimination of OHSS and no differences in pregnancy rates in recipients (four studies, OR 0.86, 95%CI 0.58-1.26; I2 = 0%). OS in OD is a safe procedure with a low rate of hospitalization after oocyte retrieval. The use of a levonorgestrel intrauterine device or a progestin contraceptive pill during OS does not impact the number of oocytes retrieved or the clinical pregnancy rate in recipients. Ultrasound monitoring seems enough for an adequate follow up of the stimulation cycle in OD. Use of fresh versus vitrified donated oocytes yielded similar pregnancy outcomes. WIDER IMPLICATIONS: This update will be helpful in the clinical management of OS in OD based on the most recent knowledge and recommendations, and possibly in the management of women under 35 years undergoing oocyte vitrification for social freezing, owing to the population similarities. More clinical research is needed on OS protocols that are specifically designed for OD, especially in term of the long-term safety for newborns, effective contraception during OS, and treatment satisfaction.

Mode of delivery of women with Swyer syndrome in a German case series.

OBJECTIVES: For women with Swyer Syndrome, a 46,XY gonadal dysgenesis, full term pregnancies are possible after oocyte donation. According to literature, mode of delivery is almost always by Caesarean section for various reasons. Medical indications are multiple pregnancies and related complications, preeclampsia, an androgynous shaped pelvis and failed induction of labor. Elective Caesarean sections were performed based on maternal request and medical recommendation. METHODS: Following careful examination and shared decision making, we planned a spontaneous delivery with a patient with Swyer syndrome and tested the different hypotheses regarding anatomical and functional features according to literature. In addition, deliveries of women with Swyer Syndrome were analyzed in a German multicenter case series. RESULTS: A total of seven women with Swyer syndrome with a total of 10 pregnancies were identified, who later gave birth to twelve live-born children. Seven out of 10 births were performed by elective and non-elective Caesarean section, three births took place vaginally. CONCLUSIONS: In summary, the risk of Caesarean section delivery has increased, but spontaneous delivery can be attempted in the event of inconspicuous findings.

High-security closed devices are efficient and safe to protect human oocytes from potential risk of viral contamination during vitrification and storage especially in the COVID-19 pandemic.

PURPOSE: The main purpose and research question of the study are to compare the efficacy of high-security closed versus open devices for human oocytes' vitrification. METHODS: A prospective randomized study was conducted. A total of 737 patients attending the Infertility and IVF Unit at S.Orsola University Hospital (Italy) between October 2015 and April 2020 were randomly assigned to two groups. A total of 368 patients were assigned to group 1 (High-Security Vitrification™ - HSV) and 369 to group 2 (Cryotop® open system). Oocyte survival, fertilization, cleavage, pregnancy, implantation, and miscarriage rate were compared between the two groups. RESULTS: No statistically significant differences were observed on survival rate (70.3% vs. 73.3%), fertilization rate (70.8% vs. 74.9%), cleavage rate (90.6% vs. 90.3%), pregnancy/transfer ratio (32.0% vs. 31.8%), implantation rate (19.7% vs. 19.9%), nor miscarriage rates (22.1% vs. 21.5%) between the two groups. Women's mean age in group 1 (36.18 ± 3.92) and group 2 (35.88 ± 3.88) was not significantly different (P = .297). A total of 4029 oocytes were vitrified (1980 and 2049 in groups 1 and 2 respectively). A total of 2564 were warmed (1469 and 1095 in groups 1 and 2 respectively). A total of 1386 morphologically eligible oocytes were inseminated by intracytoplasmic sperm injection (792 and 594 respectively, P = .304). CONCLUSIONS: The present study shows that the replacement of the open vitrification system by a closed one has no impact on in vitro and in vivo survival, development, pregnancy and implantation rate. Furthermore, to ensure safety, especially during the current COVID-19 pandemic, the use of the closed device eliminates the potential samples' contamination during vitrification and storage.

Women utilizing oocyte donation have a decreased live birth rate if they displayed a low progesterone level in a previous hormonal replacement mock cycle.

PURPOSE: Is serum progesterone(P) level on day 2 of vaginal P administration in a hormonally substituted mock cycle predictive of live birth in oocyte donation(OD)? METHODS: Retrospective analysis of 110 mock cycles from 2008 to 2016 of OD recipients having at least one subsequent embryo transfer (ET). Endometrial preparation consisted of sequential administration of vaginal estradiol, followed by transdermal estradiol and 600 mg/day vaginal micronized P. In mock cycles, serum P was measured 2 days after vaginal P introduction. OD was performed 1 to 3 years later, without P measurement. RESULTS: In mock cycles, mean serum P level on day 2 was 12.8 ± 4.5 ng/mL (range: 4-28 ng/mL). A total of 32% patients had P < 10 ng/mL. At the time of first OD, age of recipients and donors, number of retrieved and attributed oocytes, and number of transferred embryos were comparable between patients with P < 10 ng/mL in their mock cycles compared with P ≥ 10 ng/mL. Pregnancy and live birth rate after first ET were significantly lower for patients with P < 10ng/mL (9% vs. 35 %; P = 0.002 and 9% vs. 32%; P = 0.008, respectively). Considering both fresh and subsequent frozen-thawed ET, cumulative live birth rate per-patient and per-transfer were significantly lower in patients with P < 10 ng/mL in their mock cycle (14% vs. 35%; P = 0.02 and 11% vs. 27%; P = 0.03). CONCLUSION: A low P level in hormonally substituted cycles several years before ET performed with the same endometrial preparation is associated with a significantly lower chance of live birth. This suggests that altered vaginal P absorption is a permanent phenomenon. Monitoring serum P in hormonally substituted cycles appears mandatory to adjust luteal P substitution.

Significance of specialised preconception counselling in oocyte donation pregnancy with prior history of postpartum eclampsia.

A well-known complication in oocyte donation (OD) pregnancy is preeclampsia. Here, we present a 31-year-old woman, pregnant after OD. She conceived by the reception of the oocyte from her partner (ROPA) and sperm from a sperm donor. She developed preeclampsia with severe features, necessitating caesarean delivery at 29 weeks' gestation due to deterioration of her clinical condition. Admission at the intensive care unit postpartum was necessary, because of recurrent postpartum eclampsia and administration of high dose magnesium sulphate for convulsion prophylaxis. This case illustrates the importance of preconception counselling for patients who are considering to conceive by OD and double gamete donation. In this specific case an alternative way to conceive was available. However, ROPA was preferred as part of shared lesbian motherhood. The risk of complications in the subsequent pregnancy has led to an alternative decision to accomplish a second pregnancy.

'Two countries-two labs': the transnational gamete donation (TGD) programme to support egg donation.

PURPOSE: To evaluate the effectiveness, efficiency, and safety of a transnational gamete donation (TGD) programme based on the shipping of vitrified donor oocytes. METHODS: A retro-prospective observational study was conducted in the Assisted Reproductive Technology Center of the University Hospital of Florence, Italy. The study population included 622 consecutive donor oocyte cycles. A mean number of 6 vitrified oocytes per couple were shipped from two Spanish biobanks. In the receiving centre, gametes were warmed and inseminated and the subsequent embryo transfer (ET) was performed. The main outcome measurement was LBR. Secondary outcomes included oocyte survival rate, ICSI damage rate, normal fertilization, cleavage, and implantation rate (IR) in both 'fresh' and cryotransfer cycles. RESULTS: A total number of 3536 mature oocytes were warmed with 81.4% surviving oocytes. 2PN oocytes were 1941 with an ICSI normal fertilization rate of 70.4% and a cleavage rate of 93.4%; 857 day-3 embryos were transferred in 498 women, 63 blastocysts in 44. Couples with at least one vitrified embryo were 181 (32.3%). IR was 25.1% and 33.1% for day-3 ET and blastocyst stage respectively. Crude pregnancy rate and LBR after the first ET were 35.5% and 27% correspondingly with a conservative cumulative LBR of 34% and an optimal LBR of 51.4%. CONCLUSION: Imported vitrified donor oocytes retain their competence and are capable of resulting in ongoing pregnancies and healthy babies in a proportion comparable to other existing systems as egg donation with vitrification/warming in the same laboratory and transnational fresh oocyte donation.

Ovarian stimulation outcomes among transgender men compared with fertile cisgender women.

PURPOSE: To compare assisted reproductive technology (ART) outcomes among transgender men with those of fertile cisgender women. METHODS: This retrospective cohort study included 12 transgender men, six with no testosterone exposure and six after testosterone treatment, and 12 cisgender women (oocyte donors) who underwent ART in our institution between June 2017 and December 2019. Statistical analyses compared ART data and outcomes between three groups: cisgender women, transgender men without testosterone exposure, and transgender men after testosterone exposure. Comparisons were also made between transgender men with and without testosterone exposure. RESULTS: The transgender men with no testosterone exposure (23.3 ± 4 years) were significantly younger than the transgender men who had undergone testosterone treatment (30.3 ± 3.8 years; P = 0.012) and the cisgender women (29.1 ± 3.1 years; P = 0.004). The amount of FSH used for ovulation induction (1999 ± 683 mIU/mL) was significantly lower among transgender men without prior testosterone exposure compared with that among cisgender women (3150 ± 487 mIU/mL; P = 0.007). There were no differences in the peak estradiol levels, the number of oocytes retrieved, the number of MII oocytes, and the oocyte maturity rates between the three groups. Five out of six testosterone-treated transgender men underwent embryo cryopreservation, and they all achieved good-quality embryos. CONCLUSIONS: Transgender men have an excellent response to ovulation stimulation even after long-term exposure to testosterone. Oocyte/embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

Evaluation of the safety and efficacy of corifollitropin alfa combined with GnRH agonist triggering in oocyte donation cycles. A prospective longitudinal study.

OBJECTIVE: In order to help make the dream of parenthood come true for oocyte acceptors, it is essential that the procedure is not dangerous or unpleasant for oocyte donors. The aim of this study was to identify differences in safety, efficacy and patient acceptability between a traditional stimulation antagonist protocol with recombinant-FSH (rFSH) with hCG-triggering, compared with an innovative antagonist protocol with corifollitropin alfa (Elonva®) plus GnRH agonist triggering in oocyte donors. METHODS: A prospective longitudinal study was conducted at an in vitro fertilization center in Greece. The same eighty donors underwent two consecutive antagonist stimulation schemes. Primary outcomes were patient satisfaction (scored by a questionnaire) and delivery rate per donor. Secondary outcomes were mean number of cumulus-oocyte-complexes, metaphase II (MII) oocytes and ovarian hyperstimulation syndrome (OHSS) rate. RESULTS: Donors reported better adherence and less discomfort with the corifollitropin alpha + GnRH agonist-triggering protocol (p<0.001). No significant differences were identified in the clinical pregnancy rate per donor (p=0.13), the delivery rates, the number of oocytes (p=0.35), the number of MII oocytes (p=0.50) and the number of transferred embryos, between the two protocols. However, the luteal phase duration was significantly shorter (p<0.001) in the corifollitropin alpha + GnRH agonist-triggering protocol. Moreover, three cases of moderate OHSS (3.75%) were identified after hCG triggering, whereas no case of OHSS occurred after GnRH agonist ovulation induction (p=0.25). CONCLUSION: The use of corifollitropin alpha combined with a GnRH agonist for triggering is a safe, effective and acceptable protocol for oocyte donors.

Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies.

Molar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in the NLRP7 gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in the NLRP7, KHDC3L or PADI6 genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge.