Prospective multicenter observational real-world study to assess the use, efficacy and safety profile of follitropin delta during IVF/ICSI procedures (DELTA Study).

OBJECTIVE: To describe the use, efficacy and safety profile of follitropin delta in women undergoing IVF/ICSI in routine clinical practice after one treatment cycle. STUDY DESIGN: This was a French multicenter, prospective, observational study conducted in 14 fertility centers between June 2020 and June 2021. During this period, 248 women undergoing IVF or ICSI were treated with follitropin delta for the first time. Women were followed up to 10-11 weeks after the first fresh or frozen embryo transfer. The main outcomes were use of dosing algorithm, follitropin delta dosing patterns, ovarian response, pregnancy, and adverse drug reactions in routine clinical practice. RESULTS: The analyzable population consisted of 223 patients with mean ± SD age of 33.0 ± 4.4 years, body weight of 65.7 ± 11.8 kg, and the median (IQR) AMH level was 2.6 (1.5-4.0) ng/mL. For 193 patients (86.5 %) it was the first IVF/ICSI cycle and for 30 (13.5 %) the second. The algorithm was used for the calculation of the starting dose for 88.3 % of the patients. The mean daily starting dose of follitropin delta was 11.4 ± 4.1mcg for the whole analyzable population and 14.4 ± 5.2 mcg for the sub-group of 26 patients dosed without the algorithm. The mean duration of stimulation with follitropin delta was 10.8 ± 5.2 days. The mean total dose of follitropin delta administered was 122.2 ± 80.0 mcg. An antagonist protocol was used in 90.3 % of patients. The mean ± SD number of oocytes retrieved among patients that started stimulation was 11.3 ± 6.8 and 46.1 % of patients achieved the targeted response of the algorithm of 8-14 oocytes retrieved. A fresh transfer was performed for 77.6 % of patients; the mean ± SD number of embryos transferred was 1.3 ± 0.5. The implantation rate was 36.0 %. Per started cycle, clinical pregnancy was reported in 35.0 % of the patients and ongoing pregnancy in 29.6 %. In total, 5 patients (2.2 %) reported an event of OHSS. CONCLUSION: Clinical results as collected in routine clinical practice are promising, showing a favorable effectiveness-safety profile of follitropin delta for a very varied patient population (including anovulatory PCOS, very poor responders, or non-IVF naïve patients). These real-world data complement results from clinical trials and provide useful information for usual clinical practice within a heterogeneous population group.

Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer.

Progesterone (P4) is essential for pregnancy. A controlled ovarian stimulation (COS) leads to a iatrogenic luteal defect that indicates a luteal phase support (LPS) at least until pregnancy test day. Some clinicians continue the LPS until week 8 or later, when P4 is mainly secreted by syncytiotrophoblast cells.Measuring serum P4 on pregnancy test day after a fresh embryo transfer could help to identify women who might benefit from prolonged LPS. In women with LPS based on P4 administered by the rectal route, P4 concentration on pregnancy test day was significantly higher in patients with ongoing pregnancy than in patients with abnormal pregnancy.This monocentric retrospective study used data on 99 consecutive cycles of COS, triggered with human chorionic gonadotropin, followed by fresh embryo transfer resulting in a positive pregnancy test (>100 IU/L) (from November 2020 to November 2022). Patients undergoing preimplantation genetic screening or with ectopic pregnancy were excluded. All patients received standard luteal phase support (i.e. micronized vaginal progesterone 600 mg per day for 15 days). The primary endpoint was P4 concentration at day 15 after oocyte retrieval (pregnancy test day) in women with ongoing pregnancy for >12 weeks and in patients with miscarriage before week 12 of pregnancy.The median P4 concentration [range] at pregnancy test day was higher in women with ongoing pregnancy than in women with miscarriage (55.9 ng/mL [11.6; 290.6] versus 18.1 ng/mL [8.3; 140.9], p = 0.002). A P4 concentration ≥16.5 ng/mL at pregnancy test day was associated with higher ongoing pregnancy rate (OR = 12.5, 95% CI 3.61 - 43.33, p <0.001). A P4 concentration ≥16.5 ng/mL at pregnancy test day was significantly associated with higher live birth rate (OR = 11.88, 95% CI 3.30-42.71, p <0.001).After COS and fresh embryo transfer, the risk of miscarriage is higher in women who discontinue luteal support after 15 days, as recommended, but with P4 concentration <16.5 ng/mL. The benefit of individualized prolonged luteal phase support should be evaluated.

Long-term quality of life after surgical Essure removal for device-attributed symptoms.

OBJECTIVE: To analyze quality of life(QoL) and symptom resolution after surgical removal of Essure devices. METHODS: Single-center cohort study which included patients with Essure removal between February 2017 and March 2018. Surgery was performed in 65 patients by laparoscopy (Salpingectomy only or Hysterectomy). Questionnaires were used to assess QoL(SF-36), emotional disorders(HAD) and symptoms preoperatively, at 3 months and 4 years postoperatively. RESULTS: 4(6,1%) and 16(24,6%) patients were lost of follow-up at three months and 4 years postoperatively respectively. Four(6,1%) intraoperative surgical complications occurred. During the three-months postoperative period, 3(4,6%) complications occurred: five Clavien Dindo Grade 1 complications (umbilical hematoma) and one Grade 2 complication (hyperthermia and digestive disorder requiring antibiotic therapy). Preoperative QoL scores were lower than those of general population. Scores were significantly improved at 3 months and 4 years postoperatively. At 4 years postoperatively, 17/49(34,7%) had a complete regression of symptoms, 21/49(42,8%) partial resolution and 11/49(22,4%) no improvement. 27/49(55,1%) patients made the connection between symptoms and ESSURE device after media coverage. 22/49(44,89 %) were influenced by media coverage in their decision of surgery. There was a higher percentage of patients with anxiety disorder before Essure removal than 4 years after [22/44 (50 %) versus 11/44 (25 %); p = 0.0045]. CONCLUSION: Essure removal has a restorative role in terms of QoL in short and long-term. Patients should be informed about possibility of no improvement after surgery and surgical morbidity. Larger prospective cohort is needed to make a well-considered decision about risks of surgery compared with expected benefits.

Individualized luteal phase support based on serum progesterone levels in frozen-thawed embryo transfer cycles maximizes reproductive outcomes in a cohort undergoing preimplantation genetic testing.

Introduction: Low serum progesterone concentration on frozen embryo transfer (FET) day in hormone replacement therapy (HRT) cycles results in lower reproductive outcomes. Recent studies showed the efficiency of a "rescue protocol'' to restore reproductive outcomes in these patients. Here, we compared reproductive outcomes in HRT FET cycles in women with low serum progesterone levels who received individualized luteal phase support (iLPS) and in women with adequate serum progesterone levels who underwent in vitro fertilization for pre-implantation genetic testing for structural rearrangements or monogenic disorders. Design: This retrospective cohort study included women (18-43 years of age) undergoing HRT FET cycles with pre-implantation genetic testing at Montpellier University Hospital between June 2020 and May 2022. A standard HRT was used: vaginal micronized estradiol (6mg/day) followed by vaginal micronized progesterone (VMP; 800 mg/day). Serum progesterone was measured after four doses of VMP: if <11ng/ml, 25mg/day subcutaneous progesterone or 30mg/day oral dydrogesterone was introduced. Results: 125 HRT FET cycles were performed in 111 patients. Oral/subcutaneous progesterone supplementation concerned 39 cycles (n=20 with subcutaneous progesterone and n=19 with oral dydrogesterone). Clinical and laboratory parameters of the cycles were comparable between groups. The ongoing pregnancy rate (OPR) was 41.03% in the supplemented group and 18.60% in the non-supplemented group (p= 0.008). The biochemical pregnancy rate and miscarriages rate tended to be higher in the non-supplemented group versus the supplemented group: 13.95% versus 5.13% and 38.46% versus 15.79% (p=0.147 and 0.182 respectively). Multivariate logistic regression analysis found that progesterone supplementation was significantly associated with higher OPR ​​ (adjusted OR = 3.25, 95% CI [1.38 - 7.68], p=0.007). Conclusion: In HRT FET cycles, progesterone supplementation in patients with serum progesterone concentration <11 ng/mL after four doses of VMP significantly increases the OPR.

"Short agonist stop" protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study.

Introduction: Poor responder patients remain a challenge in assisted reproductive technologies. The "short agonist stop" (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria. Design: This therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients' previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6). Results: 63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer. Conclusion: SAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.

Molecular Characterization of a Rare Case of Monozygotic Dichorionic Diamniotic Twin Pregnancy after Single Blastocyst Transfer in Preimplantation Genetic Testing (PGT).

Preimplantation genetic testing (PGT) is widely used to select unaffected embryos, increasing the odds of having a healthy baby. During the last few decades, it was accepted that monozygotic dichorionic diamniotic twin pregnancies occurred from the embryo splitting before Day 3 postfertilization according to Corner's dogma. Hence, the occurrence of a dichorionic diamniotic twin pregnancy after a single blastocyst transfer was considered a dizygotic pregnancy resulting from blastocyst transfer and concurrent natural fertilization. In our study, we have provided for the first time molecular proof that a single blastocyst transfer can result in a monozygotic dichorionic diamniotic twin pregnancy, invalidating Corner's dogma. In this case, we recommend systematically assessing the genetic status of dichorionic twins after single blastocyst transfer using prenatal diagnosis to exclude the risk from a potential concurrent spontaneous pregnancy and to ensure that both fetuses are unaffected. To achieve this goal, we have developed here an innovative noninvasive prenatal diagnosis by exclusion of paternal variants with droplet digital PCR, maximizing the reliability of genetic diagnosis. Further multicentric prospective studies using genetic testing are now required to establish the rate of blastocyst splitting leading to dichorionic pregnancy in PGT and to identify the risk factors.

Fertility preservation in patients of childbearing age treated for breast cancer: A nationwide cohort study.

BACKGROUND: Approximately 7% of breast cancers are diagnosed in women under 40. Question of subsequent fertility has become fundamental. We aimed to evaluate the rate of fertility preservation (FP) by oocyte retrieval (OR) after ovarian stimulation in patients of childbearing age, managed for breast cancer with adjuvant chemotherapy in France, reuse rate of frozen gametes and live births rate (LBR) after treatment. METHODS: We included 15,774 women between 18 and 40 years old, managed by surgery and adjuvant chemotherapy for breast cancer, between January 2011 and December 2020 from a French health registry. Patients with OR after breast surgery and before chemotherapy were considered as FP group; those with no OR as no FP group. To compare LBR with French population independently of age, we calculated Standardized Incidence Rates (SIR) of live births using indirect standardization method. RESULTS: FP rate increased gradually since 2011, reaching 17% in 2019. A decrease in use was observed in 2020 (13,9%). Among patients with at least 2 years of follow-up, gamete reuse rate was 5,6%. Births after cancer were mostly from spontaneous pregnancies. Among patients with at least 3 years of follow-up, LBR was 19,6% in FP group, 3,9% in second group. SIR of live births was of 1,05 (95% CI = 0.91-1.19) and 0.33 (95% CI = 0.30-0.36) in FP and no FP group respectively. CONCLUSION: Oncofertility activity increased until 2019 in France, reaching 17%. Gamete reuse rate was low. Births resulted mainly from spontaneous pregnancies. SIR of live births was lower in no FP group.

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses.

Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62-0.84 and 0.73; 95% CI 0.59-0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17-1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6-92.0) and 272.4 (95% CI 10.8-533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139019, identifier 139019.

Whole-genome analysis of a putative rare and complex interchromosomal reciprocal insertion: thorough investigations for a straightforward interpretation.

RESEARCH QUESTION: Should whole-genome investigations be considered systematically before a complex chromosomal abnormality preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR) management is carried out using conventional cytogenetic techniques? DESIGN: A male carrying a putative rare interchromosomal reciprocal insertion (IRI) 46,XY,ins(14;?)(q11;?).ish der(14)ins(14;22)(q11.2;q11.2q11.2)(xcp14+,xcp22+,N25+,3'TRA/D+),der(22)ins(22;14)(q11.2;q11.2q11.2)(xcp22+,xcp14+,N25-,5'TRA/D+), and his partner were referred to our centre for preimplantation genetic testing analysis after three spontaneous miscarriages. Whole-genome sequencing was used to distinguish between the proposed IRI and an alternative explanation of reciprocal translocation. Fluorescence in-situ hybridization was used to detect all chromosome segments involved in this chromosomal rearrangement, to identify transferable normal and balanced embryos. RESULTS: Whole-genome sequencing allowed the determination of the number of chromosomal breakpoints involved in chromosomal rearrangement between chromosomes 14 and 22. Finally, only two breakpoints were identified instead of four in IRI rearrangements, which suggests a reciprocal translocation rearrangement. A probe strategy was established to highlight all chromosomal imbalances, whether IRI or reciprocal translocation, and preimplantation genetic testing cycles were achieved. CONCLUSION: Conventional cytogenetic techniques are not capable of identifying all complex chromosomal rearrangements, especially those involving centromeric regions and short arms of acrocentric chromosomes. The advent of new sequencing technologies has allowed for a better appreciation of genome complexity. In this study, whole-genome analysis provided additional information to explain the occurrence of genomic events and confirmed that the initial diagnosis of IRI identified by conventional cytogenetic techniques was, in fact, a simple reciprocal translocation. A reliable PGT-SR strategy was proposed for this couple to achieve their parental project.

Biphasic (5-2%) oxygen concentration strategy significantly improves the usable blastocyst and cumulative live birth rates in in vitro fertilization.

Oxygen (O2) concentration is approximately 5% in the fallopian tube and 2% in the uterus in humans. A "back to nature" approach could increase in vitro fertilization (IVF) outcomes. This hypothesis was tested in this monocentric observational retrospective study that included 120 couples who underwent two IVF cycles between 2014 and 2019. Embryos were cultured at 5% from day 0 (D0) to D5/6 (monophasic O2 concentration strategy) in the first IVF cycle, and at 5% O2 from D0 to D3 and 2% O2 from D3 to D5/6 (biphasic O2 concentration strategy) in the second IVF cycle. The total and usable blastocyst rates (44.4% vs. 54.8%, p = 0.049 and 21.8% vs. 32.8%, p = 0.002, respectively) and the cumulative live birth rate (17.9% vs. 44.1%, p = 0.027) were significantly higher with the biphasic (5%-2%) O2 concentration strategy. Whole transcriptome analysis of blastocysts donated for research identified 707 RNAs that were differentially expressed in function of the O2 strategy (fold-change > 2, p value < 0.05). These genes are mainly involved in embryo development, DNA repair, embryonic stem cell pluripotency, and implantation potential. The biphasic (5-2%) O2 concentration strategy for preimplantation embryo culture could increase the "take home baby rate", thus improving IVF cost-effectiveness and infertility management.

Corpus luteum score, a simple Doppler examination to prognose early pregnancies.

OBJECTIVES: In early pregnancies, miscarriages and inconclusive ultrasound scans considering location and viability are very common. In several previous studies, serum progesterone levels predicted viability of pregnancy and, in recent ones, failed Pregnancies of Unknown Location (PUL), completion of miscarriage and complications. Corpus luteum, secreting progesterone in early pregnancy, was less studied. Some publications showed correlations between corpus luteum aspects and diagnosis of miscarriage but it was not evaluated for other outcomes in early pregnancy, such as failed PUL, completion of miscarriage or complications. We aimed to assess if Doppler examination of corpus luteum could also predict all these outcomes: failed PUL, diagnosis and completion of miscarriages and complications. STUDY DESIGN: A single operator prospectively described and/or collected pictures of Doppler signal in the wall of the corpus luteum at most consultations in our early pregnancy unit and established a three-level score. All suspected or confirmed non-viable pregnancies with this score or/and serum progesterone levels were registered retrospectively. With logistic regressions, AIC/BIC, likelihood ratios, ROC curves, Mann-Whitney and Fisher exact tests, we evaluated the ability of the score, alone, to predict failed PUL, diagnosis and completion of miscarriages and the complications, and, combined, to improve previously published predictions. RESULTS: From 277 included pregnancies, 186 (67.1 %) miscarried. Of these, 159/186 (85.5 %) fully evacuated without surgery: 114/186 (61.3 %) within 20 days after the first diagnosis and 45/186 (24.2 %) after more than 20 days. Twenty-seven patients (14.5 %) underwent surgical evacuation, including ten complications, five haemorrhages and five suspected infections. Logistic regression correlated strongly the corpus luteum score with failed PUL (p < 0.0001) and miscarriages (p < 0.0001). Moreover, rates of complications and swift non-surgical completions of miscarriage were respectively 0 % and 92 % with scores of 0, versus 6 % and 44 % with scores of 1, versus 16 % and 0 % with scores of 2. Combined with serum progesterone levels, this score improved most predictions. Adding parity or history of miscarriage in predictive models even increased these performances. CONCLUSIONS: Corpus luteum score, alone, can predict failed PUL, diagnosis and completion of miscarriages and their complications. Combining this score with other factors (mainly serum progesterone levels) improves most predictions.

Understanding Chromosome Structure During Early Mouse Development by a Single-Cell Hi-C Analysis.

Over the past two decades, the development of chromosome conformation capture technologies has allowed to intensively probe the properties of genome folding in various cell types. High-throughput versions of these C-based assays (named Hi-C) have released the mapping of 3D chromosome folding for the entire genomes. Applied to mammalian preimplantation embryos, it has revealed a unique chromosome organization after fertilization when a new individual is being formed. However, the questions of whether specific structures could arise depending on their parental origins or of their transcriptional status remain open. Our method chapter is dedicated to the technical description on how applying scHi-C to mouse embryos at different stages of preimplantation development. This approach capitalized with the limited amount of material available at these developmental stages. It also provides new research avenues, such as the study of mutant embryos for further functional studies.

Impact of Women Obesity and Obesity Severity on Live Birth Rate after In Vitro Fertilization.

Access to in vitro fertilization (IVF) for obese women varies across centers, and the impact of obesity on IVF outcomes is widely discussed. We assessed the impact of obesity and its severity on live birth rate (LBR) after IVF. We included women treated for IVF in our center. Data were prospectively collected in the BabySentryTM software. LBR per cycle and cumulative LBR including all attempts of the couple were calculated, considering transfer of both fresh and frozen embryos. Of 1588 included women (2379 controlled ovarian stimulations), 70.2%, 19.5%, 7.9%, and 2.4% were normal-weight, overweight, class I obesity, and class II/III obesity, respectively. For each cycle, LBR did not differ according to BMI category. Adjusted odds ratios (95% confidence intervals) for obtaining a live birth at the first cycle were 1.11 (0.78-1.58) for overweight, 1.17 (0.70-1.95) for class I obese, and 1.05 (0.48-2.31) for class II/III obese women, as compared with normal-weight women. Similarly, no significant associations were found at cycles 2, 3, and 4. Cumulative LBR increased with the number of cycles, independently of the BMI class (p log-rank = 0.91). After adjustment, obesity status did not impact significantly the miscarriage rate, regardless of the cycle. In conclusion, neither women obesity nor its severity impacted the cumulative LBR after IVF.

Are ovarian response and pregnancy rates similar in selected FMR1 premutated and mutated patients undergoing preimplantation genetic testing?

PURPOSE: To assess if the ovarian response of FMR1 premutated women undergoing preimplantation genetic testing (PGT) for Fragile X syndrome is lower compared with fully mutated patients, due to their frequent premature ovarian failure. METHODS: In a retrospective cohort study from January 2009 to March 2019, we compared PGT outcomes in 18 FMR1 premutated women and 12 fully mutated women and aimed to identify predictive factors of stimulation outcomes. RESULTS: Eighty-six IVF/PGT-M cycles for FMR1 PGT were analyzed. Premutation and full mutation patients were comparable in terms of age, body mass index (BMI), basal FSH, antral follicular count, and cycle length. However, premutation carriers had significantly lower AMH (1.9 versus 4.0 ng/mL, p = 0.0167). Premutated patients required higher doses of FSH (2740 versus 1944 IU, p = 0.0069) but had similar numbers of metaphase II oocytes (7.1 versus 6.6, p = 0.871) and embryos (5.6 versus 4.9, p = 0. 554). Pregnancy rates (37.1% versus 13.3%, p = 0.1076) were not statistically different in both groups. CONCLUSION: In spite of lower ovarian reserve and thanks to an increased total dose of FSH, FMR1 premutated selected patients seem to have similar ovarian response as fully mutated patients. Neither the number of CGG repeats in FMR1 gene nor FMR1 mutation status was good predictors of the number of retrieved oocytes.

Parental-to-embryo switch of chromosome organization in early embryogenesis.

Paternal and maternal epigenomes undergo marked changes after fertilization1. Recent epigenomic studies have revealed the unusual chromatin landscapes that are present in oocytes, sperm and early preimplantation embryos, including atypical patterns of histone modifications2-4 and differences in chromosome organization and accessibility, both in gametes5-8 and after fertilization5,8-10. However, these studies have led to very different conclusions: the global absence of local topological-associated domains (TADs) in gametes and their appearance in the embryo8,9 versus the pre-existence of TADs and loops in the zygote5,11. The questions of whether parental structures can be inherited in the newly formed embryo and how these structures might relate to allele-specific gene regulation remain open. Here we map genomic interactions for each parental genome (including the X chromosome), using an optimized single-cell high-throughput chromosome conformation capture (HiC) protocol12,13, during preimplantation in the mouse. We integrate chromosome organization with allelic expression states and chromatin marks, and reveal that higher-order chromatin structure after fertilization coincides with an allele-specific enrichment of methylation of histone H3 at lysine 27. These early parental-specific domains correlate with gene repression and participate in parentally biased gene expression-including in recently described, transiently imprinted loci14. We also find TADs that arise in a non-parental-specific manner during a second wave of genome assembly. These de novo domains are associated with active chromatin. Finally, we obtain insights into the relationship between TADs and gene expression by investigating structural changes to the paternal X chromosome before and during X chromosome inactivation in preimplantation female embryos15. We find that TADs are lost as genes become silenced on the paternal X chromosome but linger in regions that escape X chromosome inactivation. These findings demonstrate the complex dynamics of three-dimensional genome organization and gene expression during early development.

Closed vitrification system and egg donation: Predictive factors of oocyte survival and pregnancy.

Although many studies have demonstrated the superiority of ultra-fast freezing compared with slow freezing, the debate is still ongoing concerning the best type of vitrification method: direct exposure to liquid nitrogen (i.e., open systems), or sterile system without contact with liquid nitrogen (i.e., closed systems). The aims of this study were to share our experience on closed vitrification systems in the framework of our egg donation programme with fully asynchronous cycles, and to identify predictive factors of successful outcome in this context. Logistic regression analysis indicated that the number of vitrified oocytes was the only factor predictive of the oocyte survival rate and of clinical pregnancy. The addition of one vitrified oocyte increased by 15 % the odds of oocyte survival. When the oocyte survival rate was considered as a continuous variable, the following results were obtained: 7 % of clinical pregnancy probability for 50 % survival rate, 15 % for 75 % survival rate, and 32 % for 100 % survival rate. The rates of oocyte survival and fertilization, embryo implantation, and clinical pregnancy were in agreement with the recommended values established by ALPHA Scientists in Reproductive Medicine in 2012. On the basis of these results, and according to the European directives on safety, we validate the routine use of closed oocyte vitrification systems for egg donation programmes. These results must be confirmed in larger samples before extrapolation to all patient types.

Fertility and obstetrical outcomes after robot-assisted laparoscopic myomectomy.

OBJECTIVE: To evaluate fertility after robot-assisted laparoscopic myomectomy (RALM) in terms of pregnancy rates, and obstetrical outcomes. PATIENTS: This is a retrospective cohort of RALM performed for symptomatic leiomyomas among women who want to conceive. Medical data were retrospectively reviewed. An office hysteroscopy was prescribed 3 months after the surgery. RESULTS: Fifty-three patients were included. The mean number of myomas was 2 ± 1.5 with a mean size of 69 ± 17.7 mm. A breach of the cavity was noticed in 15.1% of the cases. Two cases of intrauterine adhesions were diagnosed and treated during the post-operative office hysteroscopy (5.7%). Clinical pregnancy rates were 52.8% with a live birth rate of 41.5% in patients desiring pregnancy. A caesarean section was performed in 17 cases (70.8%). No case of uterine rupture was reported. CONCLUSION: More than half of the patients became pregnant after RALM. A low rate of obstetrical complications was reported, with no uterine ruptures, highlighting the promise of this technique for infertile patients.