Pregnancy outcomes in women with primary ovarian insufficiency in assisted reproductive technology therapy: a retrospective study.

Purpose: This study aims to retrospectively estimate cumulative reproductive outcomes in women with primary ovarian insufficiency (POI) in assisted reproductive technology (ART) therapy. Methods: A total of 139 patients diagnosed with POI were reviewed in this study. Firstly, they were divided into two groups according to oocyte origin: using their own oocytes (OG group) or accepting oocyte donations (OD I group). Secondly, the patients were split depending on the pregnancy outcome. In the OG group, nine patients decided to use others' oocytes after a failure of attempting to use their own, and this population was the oocyte donation II group (OD II group). Results: There were 88 patients who used their own oocytes, while 51 patients accepted oocyte donations. In the OG group, there are only 10 (7.2%) patients who got pregnant, and patients in the OD group had worse hormone levels (FSH 71.37 ± 4.18 vs. 43.98 ± 2.53, AMH 0.06 ± 0.04 vs. 1.15 ± 0.15, and AFC 0.10 ± 0.06 vs. 1.15 ± 0.15) and more years of infertility (5.04 ± 0.48 vs. 3.82 ± 0.30), which explained why they choose oocyte donation. In all the three groups, baseline characteristics were comparable between pregnant women and non-pregnant women. Of the 10 pregnant patients in the OG group, four of them used luteal-phase short-acting long protocol and had pregnancies successfully in their first cycles. Conclusion: Ovarian stimulation in POI women requires more cost and time. For those with a stronger desire to have genetic offspring, luteal-phase short-acting long protocol may help them obtain pregnancy rapidly.

Embryos from vitrified vs. fresh oocytes in an oocyte donation program: a comparative morphokinetic analysis.

OBJECTIVE: To compare the morphokinetic patterns of human embryos originating from vitrified oocytes (VITRI group) with those derived from freshly collected oocytes (CONTROL group) in oocyte donation cycles. DESIGN: This is a retrospective observational study. SETTING: Embryolab Fertility Clinic, Embryology Lab, Thessaloniki, Greece. PATIENT(S): The study included embryos from 421 vitrified oocytes from 58 oocyte donation cycles and 196 fresh oocytes from 23 oocyte donation cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Key time parameters, dynamic events, fertilization rates, degeneration rates, cleavage rates, blastocyst rates, pregnancy rates, clinical pregnancy rates, implantation rates, and live birth rates were estimated. RESULTS: The mean survival rate of vitrified oocytes was 92.58% (±7.42%). Fertilization rates were significantly different between the 2 groups (VITRI group: 71.92% ± 20.29% and CONTROL group: 80.65% ± 15.22%) whereas the degeneration, cleavage, blastocyst, pregnancy, clinical pregnancy, ongoing pregnancy, implantation, and live birth rates were not significantly different between embryos derived from fresh or vitrified oocytes. Time-lapse analysis showed no significant difference in any key time parameter. However, when examining dynamic parameters, first cell cycle (CC1) (t2 - tPB2: from the second polar body extrusion (tPB2) up to 2 cells (t2)) showed a significant difference whereas CC1a (t2 - tPNf: from fading of the pronuclei (tPNf) up to 2 cells (t2)) was at the threshold of significance. CONCLUSION(S): CC1 in vitrified oocytes exhibited a comparatively slower progression in contrast to fresh oocytes. Conversely, CC1a in vitrified oocytes demonstrated faster progression compared with fresh oocytes. It is worth noting that these temporary deviations had minimal impact on the subsequent development. Despite the clinical outcomes showing a decrease in the vitrified group, none of them reached statistical significance. This lack of significance could be attributed to the limited sample size of the study.

The impact of (very) young donor age on euploid rates: An analysis of 1831 trophectoderm biopsies evaluated with 24-chromosome NGS screening in oocyte donation cycles.

RESEARCH QUESTION: Conflicting data exists regarding whether a younger age of donors has a negative influence on the outcomes of oocyte donation cycles. Is there any correlation between a younger age of donors and the rate of embryonic aneuploidy in oocyte donation cycles? DESIGN: Retrospective study including 515 oocyte donation cycles carried out between February 2017 and November 2022. Comprehensive chromosomal screening was performed on 1831 blastocysts. 1793 had a result which were categorised into groups based on the age of the donor: 18-22 (n = 415), 23-25 (n = 600), 26-30 (n = 488), and 31-35 years (n = 290). The analysis aimed to determine the percentage of biopsy samples that were euploid and the number that were aneuploid, relative to the age group of the oocyte donor. Additionally, linear regression was employed to examine the relationship between age and the proportion of aneuploid embryos, while controlling for relevant variables. RESULTS: Aneuploidy increased predictably with donor age: 18-22 years: 27.5 %; 23-25 years: 31.2 %; 26-30 years: 31.8 %; and 31-35 years: 38.6 %. In the donor group aged 31-35 years, a higher percentage of aneuploid embryos was observed compared to younger donors in univariate analysis (OR: 1.66, 95 % CI: 1.21-2.29, p = 0.002) and multivariate logistic analysis (OR: 2.65, 95 % CI: 1.67-4.23, p < 0.001). The rates of embryonic mosaicism revealed no significant differences. CONCLUSION: The lowest risk of embryonic aneuploidy was found among donors aged <22 years. Conversely, an elevated prevalence was evident within the donor group aged 31-35 years, in contrast to the younger cohorts. The incidence of mosaic embryos remained consistent across all age groups.

Mycoplasma hominis peritonitis after oocyte donation.

We report the case of a young, immunocompetent, non-pregnant woman diagnosed with acute abdomen 3 weeks after an ultrasound-guided transvaginal oocyte retrieval (TVOR). Peritoneal fluid, obtained during exploratory laparoscopy, yielded Mycoplasma hominis as the sole pathogen. The patient's symptoms and signs improved after 24-hour treatment with intravenous clindamycin, ampicillin and gentamycin. Complete resolution was achieved with oral doxycycline for 14 days.

Progestin primed ovarian stimulation using dydrogesterone from day 7 of the cycle onwards in oocyte donation cycles: a longitudinal study.

RESEARCH QUESTION: Does a progestin-primed ovarian stimulation (PPOS) protocol with dydrogesterone from cycle day 7 yield similar outcomes compared with a gonadotrophin-releasing hormone (GnRH) antagonist protocol in the same oocyte donors? DESIGN: This retrospective longitudinal study included 128 cycles from 64 oocyte donors. All oocyte donors had the same type of gonadotrophin and daily dose in both stimulation cycles. The primary outcome was the number of cumulus-oocyte complexes (COC) retrieved. RESULTS: The number of COC retrieved (mean ± SD 19.7 ± 10.8 versus 19.2 ± 8.3; P = 0.5) and the number of metaphase II oocytes (15.5 ± 8.4 versus 16.2 ± 7.0; P = 0.19) were similar for the PPOS and GnRH antagonist protocols, respectively. The duration of stimulation (10.5 ± 1.5 days versus 10.8 ± 1.5 days; P = 0.14) and consumption of gonadotrophins (2271.9 ± 429.7 IU versus 2321.5 ± 403.4 IU; P = 0.2) were also comparable, without any cases of premature ovulation. Nevertheless, there was a significant difference in the total cost of medication per cycle: €898.3 ± 169.9 for the PPOS protocol versus €1196.4 ± 207.5 (P < 0.001) for the GnRH antagonist protocol. CONCLUSION: The number of oocytes retrieved and number of metaphase II oocytes were comparable in both stimulation protocols, with the advantage of significant cost reduction in favour of the PPOS protocol compared with the GnRH antagonist protocol. No cases of premature ovulation were observed, even when progestin was started later in the stimulation.

Addressing Privacy Concerns Surrounding Oocyte Donation in the United States: Gone With Anonymity.

Oocyte donation has greatly expanded in the past several decades since the first procedure was performed in 1983. According to the Centers for Disease Control, the number of cycles using donor oocytes increased from 18,011 cycles in 2010 to 27,131 cycles in 2019. Oocyte donation has become an important reproductive option for women with diminished ovarian reserve, recurrent failed in vitro fertilization, or heritable genetic conditions. It is also particularly important for single men, same-sex male couples, and men with a transgender woman partner. More recently, societal changes accompanying the expansion of social media and broader access to direct-to-consumer DNA testing have raised concerns about privacy and anonymity. In this article, we review two specific aspects of donor privacy: privacy related to personal identifiers provided by clinics or donor egg bank websites and privacy related to direct-to-consumer genetic testing. We also provide clinical recommendations specific to the United States for working with oocyte donors and donor oocyte recipients.

What importance do donors and recipients attribute to the nuclear DNA-related genetic heritage of oocyte donation?

STUDY QUESTION: How do oocyte donors and recipients perceive the genetic link related to the transfer of nuclear DNA between donors and offspring? SUMMARY ANSWER: Whether they are donors or recipients, individuals attach great importance to the transmission of their genetic heritage, since 94.5% would opt for the pronuclear transfer method to preserve this genetic link in the context of oocyte donation. WHAT IS KNOWN ALREADY: Since 1983, the use of oocyte donation has increased worldwide. Performed in France since the late 1980s and initially offered to women with premature ovarian insufficiency, its indications have progressively expanded and now it is proposed in many indications to prevent the transmission of genetically inherited diseases. This has resulted in an increase in the waiting time for access to oocyte donation due to the difficulty in recruiting oocyte donors in French ART centres. Several articles have discussed how to fairly distribute donor oocytes to couples, but few have interviewed women in the general population to record their feelings about oocyte donation, as either the donor or recipient and the importance given to the genetic link between the oocyte donors and the children born. Mitochondrial replacement therapy (MRT) is a technique originally developed for women at risk of transmitting a mitochondrial DNA mutation. Recently, MRT has been considered for embryo arrest and oocyte rejuvenation as it could help females to reproduce with their own genetic material through the transfer of their oocyte nucleus into a healthy donor oocyte cytoplasm. STUDY DESIGN, SIZE, DURATION: We conducted an opinion survey from January 2021 to December 2021, during which 1956 women completed the questionnaire. Thirteen participants were excluded from the analysis due to incomplete responses to all the questions. Consequently, 1943 women were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We specifically developed a questionnaire for this study, which was created and distributed using the Drag'n Survey® software. The questionnaire consisted of 21 items presented alongside a video created with whiteboard animation software. The aim was to analyse whether certain factors, such as age, education level, marital status, number of children, use of ART for pregnancy, video viewing, and knowledge about oocyte donation, were associated with feelings towards oocyte donation, by using a univariate conditional logistic regression model. This statistical method was also used to assess whether women would be more inclined to consider oocyte donation with the pronuclear transfer technique rather than the whole oocyte donation. All parameters found to be statistically significant in the univariate analysis were subsequently tested in a multivariate model using logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Most women were concerned about the biological genetic contribution of the donated oocyte (94.8%). The most common reason for a women's reluctance to donate their oocytes was their unwillingness to pass on their genetic material (33.3%). Nearly 70% of women who were initially hesitant to donate their oocytes indicated that they would reconsider their decision if the oocyte donation was conducted using donated cytoplasm and the pronuclear transfer technique. Concomitantly, >75% of the respondents mentioned that it would be easier to receive a cytoplasm donation. The largest proportion of the population surveyed (94.5%) expressed their support for its legalization. LIMITATIONS, REASONS FOR CAUTION: In this study, a substantial portion of the responses came from individuals with medical or paramedical backgrounds, potentially introducing a recruitment bias among potential donors. The rate of missing responses to the question regarding the desire to become an oocyte donor was 13.6%, while the question about becoming an oocyte cytoplasm donor had a missing response rate of 23%. These missing responses may introduce a bias in the interpretation of the data. WIDER IMPLICATIONS OF THE FINDINGS: This study was the first to demonstrate that, for the French population studied, the combination of oocyte cytoplasm donation with pronuclear transfer could offer a promising approach to enhance the acceptance of oocyte donation for both the donor and the recipient. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

New recommendations for informing patients and gamete donors in assisted reproduction.

The number of cycles of assisted reproduction using donor body parts is increasing significantly. In Europe alone, around one hundred thousand children are born each year who have some relationship to three or more parents. The European expert guarantor European Society of Human Reproduction and Embryology therefore issued a recommendation in 2022 to inform donors, recipients and children born in this way. Our article analyses developments in this area and proposes a solution for the Czech Republic. It is necessary for providers to immediately respond to the fact that the anonymity of donation can no longer be guaranteed, and to adapt the content of consultations and informed consents of potential donors and applicants accordingly. Legislation then has two possible solutions: first to adopt a system of "polyparenthoods" or second to fundamentally limit donation cycles.

Should a gamete bank verify the non-medical information provided by a donor?

Over the years, cases of fraud have been discovered where donors have been lying about their characteristics. The question raised by such cases is what the responsibility of the gamete bank is for the non-medical information provided by the donor. The problem is that extended donor profiles contain a large amount of information about different aspects of the donor's life and that not all this information can be verified or is worth verifying. Two cases are scrutinized in more detail: education and criminal record. The proposed solution is to split the donor information into a verified and a non-verified part with the non-verified part falling under the responsibility of the donor. The question of what information should be included in the verified part of the donor profile is still open.

Live Birth After Oocyte Donation In Vitro Fertilization Cycles in Women With Endometriosis: A Systematic Review and Meta-Analysis.

Importance: Although multiple mechanisms have been proposed to explain the infertility related to endometriosis, there are no conclusive data on the association of endometriosis with endometrial receptivity. The oocyte donation model in assisted reproduction technology (ART) cycles can clarify this issue. Objective: To explore the association of a history of endometriosis with ART outcomes in recipients of oocyte donation. Data Sources: In this systematic review and meta-analysis, electronic databases were searched from inception until August 31, 2023, using combinations of relevant keywords. Moreover, we retrieved data from the databases of the Society for Assisted Reproductive Technology (SART) in the US and the Human Fertilization and Embryology Authority (HFEA) in the United Kingdom. Study Selection: Observational studies were included if they investigated the impact of endometriosis on ART outcomes with donor oocytes. Data Extraction and Synthesis: Publicly available data related to ART from various sources were gathered, and a retrospective aggregate and nonaggregate analysis using registries of in vitro fertilization cycles with oocyte or embryo donation was conducted. Main Outcomes and Measures: The primary outcome was live birth rate (LBR) following oocyte donor cycles. The effect measures of comparisons between groups are presented as odds ratios (ORs) with a 95% CI. Results: This study analyzed 7212 oocyte donation cycles from 4 studies for the meta-analysis, along with 162 082 cycles from 2 registries (137 182 from SART and 24 900 from HFEA). No significant differences between the groups were observed in the meta-analysis of published data after adjusting for confounding factors (OR, 0.54; 95% CI, 0.19-1.57). A statistically significant lower LBR was identified in women with endometriosis when analyzing the aggregate data from SART and HFEA databases (OR, 0.89; 95% CI, 0.81-0.97). Conclusions and Relevance: This study found a modest decrease in LBR among women with a history of endometriosis, although only results from the pooled analysis of registry data and not those from the meta-analysis reached statistical significance. These findings suggest that a marginal impairment of uterine receptivity may contribute to infertility mechanisms in women affected by endometriosis.

Direct-to-consumer genetic testing and the changing landscape of gamete donor conception: key issues for practitioners and stakeholders.

RESEARCH QUESTION: What effect does direct-to-consumer genetic testing (DTCGT) have on information finding and sharing in relation to gamete donor conception? DESIGN: This study used in-depth qualitative interviews with parents through donor conception, donors, the relatives of donors and donor-conceived people who have used, or considered using, DTCGT. Interviews were conducted between September 2021 and February 2023. Sixty people defined themselves as having been affected by donor conception and DTCGT. Fifty-seven of these were resident in the UK at the time of interview. The final sample included 19 (spermatozoa, egg or embryo) donors, 25 donor-conceived people, 20 parents through donor conception and two relatives of donors. Five participants occupied more than one of these roles. RESULTS: The rise of DTCGT is affecting how information about donor conception is managed: it shifts patterns of knowledge about donor conception; increases flexibility regarding the age of access to information about donor relatives; can lead to a growing role for non-professionals, including wider family members, in gatekeeping information about donor conception; accentuates the effect of donor conception for donors' and the relatives of donor-conceived people; and shapes, and is shaped, by the formal regulatory donor information management systems. CONCLUSION: Fertility professionals should inform people using, or considering, donor conception, or (potential) donors, about the different ways DTCGT can affect sharing information about donor conception. Support is needed for those affected by these changes.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

Searching for and making genetic connections: recommendations for practice from donor conceived adults in the UK.

RESEARCH QUESTION: What are the support needs of donor conceived individuals who are searching for or open to matching with genetic connections? DESIGN: A total of 88 donor conceived adults in the UK participated in an online survey open between January and August 2022. Participants were asked about their level of awareness of current resource provision, recommendations for resources to support the process of searching for genetic connections, and recommendations for resources to support with feelings about searching for or being found by genetic connections. RESULTS: Participants were found to have varying levels of awareness of the resources available to them, with 39% describing themselves as aware, 41% as partly aware and 20% as unaware. Their recommendations for practical and emotional resources also varied. The most recommended resources for practical support were DNA testing and changes to UK law. The most recommended resources for emotional support were counselling and peer and other support groups. CONCLUSIONS: The impact of legal and technological changes such as direct-to-consumer DNA testing and the legal transition to identifiable donation may be felt by donor conceived individuals irrespective of their year of birth. The wishes of donor conceived individuals for different support resources should be borne in mind by practitioners, regulatory bodies, and policy makers going forward.

Why it is important that we understand the information that gamete donors provide about themselves to recipients.

A personal description and goodwill message is often the only form of communication a gamete recipient receives from the donor. However, the nature of the information gamete donors leave for recipients is not well understood. This Viewpoint article discusses a recent study published in this journal that makes a significant contribution to our understanding of this area of research and raises important questions for research going forward.

Random-start ovarian stimulation in an oocyte donation programme: a large, single-centre, experience.

RESEARCH QUESTION: Do live birth rates differ between recipients matched with donors using conventional ovarian stimulation compared with those using random-start protocols? DESIGN: Retrospective analysis of 891 ovarian stimulations in egg donors (January-December 2018) and clinical outcomes in matched recipients (n = 935). Donors commenced ovarian stimulation on day 1-3 of the menstrual cycle (n = 223) or in the mid/late-follicular (n = 388) or luteal phase (n = 280) under a conventional antagonist protocol. Live birth rate of matched recipients was the main outcome. RESULTS: Duration of stimulation and total gonadotrophin dose were comparable between conventional versus random-start groups. The number of collected eggs were similar (17.6 ± 8.8 versus 17.2 ± 8.5, P = 0.6, respectively). Sub-group analysis showed that stimulation length (10.2 ± 1.8 versus 9.8 ± 1.7 versus 10.4 ± 1.7, P < 0.001) and gonadotrophin consumption (2041.5 ± 645.3 versus 2003.2 ± 647.3 versus 2158.2 ± 685.7 IU, P = 0.01) differed significantly between the conventional, mid/late follicular and luteal phase groups, respectively. In matched recipients receiving fresh oocytes and undergoing fresh embryo transfer, the biochemical pregnancy (63.8% and 63.3%; P = 0.9), clinical pregnancy (54.6% and 56.1%; P = 0.8) and live birth rates (47.7% and 46.6%; P = 0.7) per embryo-transfer were similar between conventional versus random groups. Similar results were obtained in recipients receiving vitrified eggs. Euploidy rate was also comparable. CONCLUSIONS: No notable variations were found in clinical outcomes using oocytes obtained from random-start protocols and those proceeding from conventional ovarian stimulation in oocyte donation treatments. Luteal-phase stimulation seems to require longer stimulation and higher FSH consumption. Random-start stimulation strategy does not impair the potential of the oocyte yield or clinical outcomes in oocyte donation cycles.