Ovarian tissue cryopreservation can be combined simultaneously with oocyte retrieval after controlled ovarian hyperstimulation.

STUDY QUESTION: Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)? SUMMARY ANSWER: Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step. WHAT IS KNOWN ALREADY: In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended. STUDY DESIGN, SIZE, DURATION: This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of >24 h (n = 5) and IVM of oocytes obtained ex vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33). PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularization and apoptosis using immunohistochemistry, when patient consent was obtained. MAIN RESULTS AND THE ROLE OF CHANCE: No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (median = 8.5 (25% = 5.3-75% = 12.0)) compared to the unstimulated group (2.0 (1.0-5.3), P < 0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, P < 0.001). COH also increased haemorrhagic suffusion (COH + OTC: 66.7%; IVM + OTC: 18.8%, P = 0.002) and oedema (COH + OTC: 55.6%; IVM + OTC: 9.4%, P < 0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 (0.33-0.85) and 0.45 (0.23-0.58) in unstimulated and stimulated groups respectively, P = 0.720). LIMITATIONS, REASONS FOR CAUTION: The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only. WIDER IMPLICATIONS OF THE FINDINGS: Unilateral oophorectomy can be successfully performed after COH with limited bleeding risk and an absence of impact on thawed OT. This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice. STUDY FUNDING/COMPETING INTEREST(S): This work was made possible through the support of the reproductive department of Antoine-Béclère Hospital and of the pathological department of Bicêtre Hospital (Assistance Publique Hôpitaux de Paris, France). The authors have no conflict of interest to disclose in this study. TRIAL REGISTRATION NUMBER: N/A.

Live birth rate after use of cryopreserved oocytes or embryos at the time of cancer diagnosis in female survivors: a retrospective study of ten years of experience.

PURPOSE: The aim of this study was to evaluate the outcomes of frozen oocytes or embryos cryopreserved after controlled ovarian stimulation (COS) or in vitro maturation (IVM) for female cancer patients who underwent a fertility preservation (FP) prior to gonadotoxic therapy. METHODS: A retrospective cohort study from 2009 to December 2017 was conducted. Among the 667 female cancer patients who underwent oocytes or embryos cryopreservation for FP, 40 (6%) have returned to the fertility clinic between 2011 and 2019 to use their frozen material after being cured. We compared these thaw cycles outcomes according to the techniques used at the time of cryopreservation. RESULTS: Among the 40 women cancer survivors who used their cryopreserved material, thirty patients have benefited from at least one embryo transfer. Ten patients did not have an embryo transfer since the oocytes did not survive after the thawing process or because no embryo was obtained after fertilization. We related three live births following FP using IVM (two from frozen oocytes and one after embryo cryopreservation). Five live births were obtained when COS was performed at the time of FP (one from frozen oocytes and four after embryo cryopreservation). CONCLUSIONS: Our preliminary results, although they are obtained in a small sample, are encouraging and show that different FP techniques can be used in female cancer patients and lead to live births. IVM is one of the options available that does not delay the start of chemotherapy or if ovarian stimulation using gonadotropins is contraindicated.

First follow-up of art pregnancies in the context of the COVID-19 outbreak.

OBJECTIVE: The aims of this study were to follow up the monitoring, health and anxiety from women who became pregnant after an embryo transfer or a intrauterine insemination during the COVID-19 epidemic in France STUDY DESIGN: This is a single centre, retrospective study from December 2019 to March 2020 based on a phone call interview using a specific questionnaire sheet specially developed for this study. Questionnaires from 104 pregnant women were completed and descriptive data are then analyzed. RESULTS: Women with ongoing pregnancies (n = 88) did not change their physician visits. The COVID-19 outbreak has created no or few additional stresses for 77 % of pregnant women since the lockdown started. We report a miscarriage rate of 14.4 % (n = 15) and documented 10 patients (11.3 %) who had symptoms related to COVID-19. No severe symptoms and no hospitalization in intensive care unit were identified. CONCLUSION: The epidemic context did not disrupt the medical monitoring of pregnancies and we did not recover an increased rate of miscarriage after ART. None of the patients who had COVID-related symptoms presented with severe clinical manifestations. Surprisingly, pregnant women were psychologically able to experience the lockdown.

Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis.

BACKGROUND: A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis. OBJECTIVE AND RATIONALE: Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed. SEARCH METHODS: A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses. OUTCOMES: A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation. WIDER IMPLICATIONS: Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.

Shortening gametes co-incubation time improves live birth rate for couples with a history of fragmented embryos.

Short gamete co-incubation (SGCO) consists in decreasing the duration of contact between oocytes and sperm from the standard overnight insemination (SOI) toward 2 hours. However, the effectiveness of this technique to improve in vitro fertilization and embryo transfer (IVF-ET) outcomes remains controversial. Our study was designed to evaluate the efficiency of SGCO in a poor prognosis population with a history of fragmented embryos defined by the presence of at least 50% of the embryos with more than 25% of cytoplasmic fragments. From January 2010 to January 2014, 97 couples were included in a SGCO protocol. We separated women into 2 subgroups: younger and older than 35 years. Compared to SOI, after SGCO, 2-cell stage embryos were higher in all women (p<0.001) and less fragmented in women over 35 years (p<0.05). On day 2, top quality embryos obtained and transferred were higher with SCGO than with SOI, independently of the age of the women (p<0.001). Moreover, the number of embryos with less than 25% of fragmentation was higher after SGCO than SOI (p<0.001) whereas the number of multinucleated embryos was lower (p<0.001). We observed that after fresh ET, independently of the age of the women, the clinical pregnancy rate was 3 times higher after SGCO than after SOI. However, the live-birth rate was 4 times higher with SGCO than with SOI in women above 35 years but 3 times higher with SGCO than with SOI in women younger than 35 years. The present results indicate that for a particular indication, reducing the time of oocytes and sperm co-incubation may improve IVF-ET outcomes in terms of live-birth rate. ABBREVIATIONS: AMH: anti mullerian hormone; COC: cumulus-oocytes complex; E2: estradiol; ET: embryo transfer; FET: frozen embryo transfer; FSH: follicle stimulating hormone; GnRH: gonadotrophin releasing hormone; hCG: human chorionic gonadotropin hormone; hMG: human menopausal gonadotropin hormone; IRB: institutional review board; IVF: in vitro fertilization; IVF-ET: in vitro fertilization and embryo transfer; MNB: multinucleated blastomere; mRNA: messanger ribonucleic acid; OC: oocyte retrieval; O2: oxygen; ROS: reactive oxygen species; SGCO: short gamete co-incubation; SOI: standard overnight insemination.

Levels of follicular G-CSF and interleukin-15 appear as noninvasive biomarkers of subsequent successful birth in modified natural in vitro fertilization/intracytoplasmic sperm injection cycles.

OBJECTIVE: To explore oocyte competence for subsequent birth. The modified natural IVF/intracytoplasmic sperm injection (ICSI) cycle was used as an experimental model by measuring levels of cytokines, chemokines, and growth factors in individual follicular fluids (FF). DESIGN: A retrospective blinded study. SETTING: European network of research, Embryo Implantation Control (EMBIC). PATIENT(S): Single FF from 83 women were analyzed during a modified natural IVF/ICSI cycle, and reproducibility of follicular composition was evaluated over two cycles for 15 patients. INTERVENTION(S): Each FF sample was blindly tested to assess levels of 26 factors by bead-based immunoassays. MAIN OUTCOME MEASURE(S): Each mediator was evaluated as a potential biomarker of subsequent birth by multivariate regression analysis. RESULT(S): A combination of both FF G-CSF and IL-15 was the optimal model to predict birth (AUC(ROC), 0.85). Birth rates per cycle were 48.9% (16/33) if two good-prognosis criteria were present (FF G-CSF>12 pg/mL and IL-15<7 pg/mL) and 8% (3/36) and 0% (0/14) if, respectively, one or none were present. FF G-CSF was significantly correlated over two cycles (r=.71), suggesting a possible prognostic value of its documentation. CONCLUSION(S): Combined follicular G-CSF and IL-15 quantification appears as an efficient and noninvasive method to define oocyte competence for subsequent successful conception in modified natural IVF/ICSI cycles.

Early follicle development during the luteal-follicular transition affects the predictability of serum follicle-stimulating hormone but not antimüllerian hormone levels on cycle day 3.

OBJECTIVE: To verify whether the presence of an overdeveloped antral follicle modifies the expected relationship between serum antimüllerian hormone (AMH), estradiol, or follicle-stimulating hormone (FSH) levels and antral follicle count on cycle day 3. DESIGN: Prospective study. SETTING: Teaching hospital, France. PATIENT(S): Two hundred seventy-seven normo-ovulating women. INTERVENTION(S): Serum AMH, estradiol, and FSH levels and the number and size of antral follicles (3 to 12 mm) were measured on cycle day 3. Two groups were set according to the presence ("large" group) or absence ("small" group) of at least one follicle measuring >7 mm. MAIN OUTCOME MEASURE(S): Hormonal-follicular correlation. RESULT(S): Whereas, as expected, the correlation between FSH and follicle counts was affected by the presence of an overdeveloped follicle, the correlation between AMH and follicle counts remained unaffected. Estradiol failed to be correlated with antral follicle counts in both groups. CONCLUSION(S): In contrast with FSH, AMH levels remain tightly correlated to the number of antral follicles despite the presence of early growing follicles on cycle day 3.

Implication of HLA-G in human embryo implantation.

The mechanisms underlying the processes of human embryo implantation and maternal immunotolerance to the fetus remain incompletely understood. Growing evidence indicates that one of the nonclassic human leukocyte antigen (HLA) genes, HLA-G, is expressed selectively on the surface of the extravillous throphoblast and plays an important role in the adaptations of the maternal immune system to pregnancy; however the implication of this molecule in the process of human embryo implantation is also plausible. Therefore the aim of the present article is to review the available literature specifically focused on the possible relationship between HLA-G and human embryo implantation. In particular, studies investigating HLA-G expression on human preimplantation embryos and in the endometrium, as well as its levels in embryo culture supernatants and circulating maternal blood, are discussed.