Mixtures of persistent organic pollutants and ovarian function in women undergoing IVF.

RESEARCH QUESTION: Do internal levels of persistent organic pollutants (POP) in serum and follicular fluid affect ovarian function of women attending IVF? DESIGN: This cohort study included 136 women undergoing IVF in the assisted reproductive technology (ART) service of University Hospital from Nantes (France). Representative POP were measured using gas and liquid chromatography coupled with tandem mass spectrometry. Polyfluoroalkylated and perfluoroalkylated substances were measured in serum and polychlorinated biphenyls and organochlorinated pesticides in follicular fluid. Statistical associations between POP and ovarian reserve markers (anti-Müllerian Hormone [AMH] and antral follicle count [AFC], and ovarian responsiveness markers (Ovarian Sensitivity Index [OSI] and Follicular Output RaTe [FORT]), were explored in single and multipollutant regression models. RESULTS: Twenty-seven out of 53 POP congeners were frequently detected in almost all women attending IVF. Adjusted models did not show statistically significant associations between POP and ovarian reserve markers. Positive associations were found between some POP, i.e. hexachlorobenzene with FORT (ß 0.42, 95% CI 0.13 to 0.71, P = 0.005) or PCB52 with Ovarian Sensitivity Index (ß 0.22; 95% CI, 0.07 to 0.38, P = 0.005). Negative associations between some polyfluoroalkylated and perfluoroalkylated substances, PCB189 and trans-nonachlor with AFC and AMH were found among current smokers. CONCLUSIONS: Globally, associations between POP and the markers of ovarian function or responsiveness were lacking. Nonetheless, the stratification analysis suggested that current smoking could be a risk modifier, and extension of the study to a larger population sample size is needed.

Heavy metals and diminished ovarian reserve: single-exposure and mixture analyses amongst women consulting in French fertility centres.

RESEARCH QUESTION: Do heavy metals affect the risk of diminished ovarian reserve (DOR) in women of reproductive age? DESIGN: A total of 139 cases and 153 controls were included between 2016 and 2020. The participants were aged between 18 and 40 years and attended consultations for couple infertility in one of four fertility centres in western France. Cases of DOR were defined as women with an antral follicle count less than 7, anti-Müllerian hormone levels 1.1 ng/ml or less, or both. Controls were frequency matched on age groups and centres, and were women with normal ovarian reserve evaluations, no malformations and menstrual cycles between 26 and 35 days. Heavy metals (lead, mercury, cadmium and chromium) were measured in whole blood at inclusion. Single-exposure associations were examined with multivariable logistic regressions adjusted on potential confounders. Mixture effects were investigated with quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Chromium as a continuous exposure was significantly associated with DOR in unadjusted models (OR 2.07, 95% CI 1.04 to 4.13) but the association was no longer significant when confounders were controlled for (adjusted OR 2.75, 95% CI 0.88 to 8.60). Similarly, a statistically significant association was observed for the unadjusted second tercile of cadmium exposure (OR 1.87, 95% CI 1.06 to 3.30); however, this association was no longer statistically significant after adjustment. None of the other associations tested were statistically significant. Quantile g-computation and BKMR both yielded no significant change of risk of DOR for the mixture of metals, with no evidence of interaction. CONCLUSIONS: Weak signals that some heavy metals could be associated with DOR were detected. These findings should be replicated in other studies.

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.

Sexual function in heterosexual couples undergoing assisted reproductive technology (ART) cycles with donor sperm.

PURPOSE: Sexuality and the desire for children are closely linked, and infertility can increase the risk of sexual dysfunction (SD). Among heterosexual infertile couples undergoing assisted reproductive technology (ART) cycles, those referred for donor sperm cycles constitute a specific subgroup, potentially different than those undergoing ART with partner's sperm, as giving up on biological parenthood can be difficult to overcome. However, the impact of donor sperm ART on infertile couples' sexuality has been hardly explored in the literature. This study aimed to describe the sexual function in couples undergoing ART with donor sperm. METHODS: This monocentric prospective observational study was conducted in heterosexual couples undergoing ART cycle with sperm donor, using the FSFI and the IIEF15 questionnaires. Seventy-nine couples were solicited to participate in the study. RESULTS: In our sample, 39.3% (n = 24) of women had sexual dysfunction (SD). Among men, 26.5% (n = 13) had erectile dysfunction (ED). No statistically significant difference was found between both groups (with or without SD) in men and women in univariate analysis. Therefore, multivariate analysis was not performed and no specific predictor of SD could be identified. CONCLUSION: Although this should be confirmed in a larger number of participants, our study demonstrates that a significant proportion of infertile patients undergoing ART with donor semen suffer from SD. No significant predictor could, however, be identified. Further research should focus on the evaluation of psychological interventions to treat or improve these disorders.

Predictive factors of effective tibial nerve release in tarsal tunnel syndrome.

BACKGROUND: Factors that may affect surgical decompression results in tarsal tunnel syndrome are not known. METHODS: A retrospective single-center study included patients who had undergone surgical tibial nerve release. The effectiveness of decompression was evaluated according to whether the patient would or would not be willing to undergo another surgical procedure in similar preoperative circumstances. RESULTS: The patients stated for 43 feet (51%) that they would agree to a further procedure in similar circumstances. Six feet with space-occupying lesions on imaging had improved results, but neurolysis failed in 9 feet with bone-nerve contact. Neurolysis was significantly less effective when marked hindfoot valgus (p = 0.034), varus (p = 0.014), or fasciitis (p = 0.019) were present. CONCLUSIONS: If imaging reveals a compressive space-occupying lesion, surgery has a good prognosis. In feet with static hindfoot disorders or plantar fasciitis, conservative treatment must be optimized. Bone-nerve contact should systematically be sought.

Time-lapse technology improves total cumulative live birth rate and shortens time to live birth as compared to conventional incubation system in couples undergoing ICSI.

PURPOSE: The improvement of clinical outcome provided by time-lapse technology (TLT) in IVF over conventional incubation (CI) still remains controversial. This study aimed at evaluating whether the exclusive use of time-lapse technology (TLT) during whole IVF care improves total cumulative live birth rate (TCLBR) and shortens time to live birth (TTLB) as compared to the use of CI in couples undergoing ICSI. METHODS: This retrospective cohort study was conducted in couples with male infertility undergoing their first ICSI cycle in 2014-2015 and for whom embryo culture system remained the same during their whole IVF care, i.e., TLT or CI. Couples were followed up up to 2020, including all following frozen-embryo transfers and ICSI cycles (if any). Survival analysis was used to compare clinical outcome and time-related endpoints between both groups. RESULTS: A total of 151 and 250 couples underwent their whole IVF care with the exclusive use of TLT and CI, respectively. Survival analysis showed that TCLBR after whole IVF care was significantly higher in TLT than in CI group (66.9 vs 56.4%, p=0.02, log-rank test). Median live birth time was significantly shorter in TLT than CI group (464 vs 596 days, p=0.01). CONCLUSIONS: We found that TCLBR and TTLB were significantly improved with TLT over CI in couples undergoing ICSI for male factor. This study fuels the debate on the clinical benefit of using TLT. The use of time-related endpoints adds important information for both patients and practitioners.

Performance of Day 5 KIDScore™ morphokinetic prediction models of implantation and live birth after single blastocyst transfer.

PURPOSE: While several studies reported the association between morphokinetic parameters and implantation, few predictive models were developed to predict implantation after day 5 embryo transfer, generally without external validation. The objective of this study was to evaluate the respective performance of 2 commercially available morphokinetic-based models (KIDScore™ Day 5 versions 1 and 2) for the prediction of implantation and live birth after day 5 single blastocyst transfer. METHODS: This monocentric retrospective study was conducted on 210 ICSI cycles with single day 5 embryo transfer performed with a time-lapse imaging (TLI) system between 2013 and 2016. The association between both KIDScore™ and the observed implantation and live birth rates was calculated, as well as the agreement between embryologist's choice for transfer and embryo ranking by the models. RESULTS: Implantation and live birth rate were both 35.7%. A significant positive correlation was found between both models and implantation rate (r = 0.96 and r = 0.90, p = 0.01) respectively. Both models had statistically significant but limited predictive power for implantation (AUC 0.60). There was a fair agreement between the embryologists' choice and both models (78% and 61% respectively), with minor differences in case of discrepancies. CONCLUSIONS: KIDScore™ Day 5 predictive models are significantly associated with implantation rates after day 5 single blastocyst transfer. However, their predictive performance remains perfectible. The use of these predictive models holds promises as decision-making tools to help the embryologist select the best embryo, ultimately facilitating the implementation of SET policy. However, embryologists' expertise remains absolutely necessary to make the final decision.

Ovarian reserve and response to stimulation in women undergoing fertility preservation according to malignancy type.

RESEARCH QUESTION: Does ovarian reserve and ovarian response to ovarian stimulation in women with cancer undergoing oocyte vitrification for fertility preservation vary according to the type of malignancy? DESIGN: Retrospective cohort study including 105 women aged between 18 and 40 years, who were referred for fertility preservation (oocyte vitrification) between 2013 and 2016. The women were divided into three groups: breast cancer, lymphoma or other cancer. All of them had been recently diagnosed with cancer, with gonadotoxic treatment scheduled, and had oocyte vitrification after ovarian stimulation with antagonist protocol. RESULTS: Baseline antral follicle count and anti-Müllerian hormone were no different between women with breast cancer, lymphoma or other cancer. The number of cancelled cycles for poor ovarian response was similar between the groups. The number of FSH units per mature oocyte, the number of mature oocytes (metaphase II) retrieved, and the oocyte maturity rate were not significantly different between the three groups. CONCLUSIONS: As the type of cancer does not seem to significantly affect ovarian reserve and ovarian response to ovarian stimulation, our results do not support the relevance of integrating this parameter when establishing ovarian stimulation protocol for oocyte vitrification cycle in women with cancer.

Use of the serum anti-Müllerian hormone assay as a surrogate for polycystic ovarian morphology: impact on diagnosis and phenotypic classification of polycystic ovary syndrome.

STUDY QUESTION: Does the use of the serum anti-Müllerian hormone (AMH) assay to replace or complement ultrasound (U/S) affect the diagnosis or phenotypic distribution of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Combining U/S and the serum AMH assay to define polycystic ovarian morphology (PCOM) diagnoses PCOS (according to the Rotterdam classification) in more patients than definitions using one or the other of these indicators exclusively. WHAT IS KNOWN ALREADY: Since 2003, PCOM, as defined by U/S, is one of the three diagnostic criteria for PCOS. As it is closely correlated with follicle excess seen at U/S, an excessive serum AMH level could be used as a surrogate for PCOM. STUDY DESIGN, SIZE, DURATION: Single-center retrospective study from a database of prospectively collected clinical, laboratory and ultrasound data from patients referred for oligo-anovulation (OA) and/or hyperandrogenism (HA) between January 2009 and January 2016. PARTICIPANTS/MATERIALS, SETTING, METHOD: The standard Rotterdam classification for PCOS was tested against two modified versions that defined PCOM by either excessive serum AMH level alone (AMH-only) or a combination (i.e. 'and/or') of the latter and U/S. The PCOS phenotypes were defined as A (full phenotype, OA+HA+PCOM), B (OA+HA), C (HA+PCOM) and D (OA+PCOM). MAIN RESULTS AND THE ROLE OF CHANCE: PCOS was more frequently diagnosed when PCOM was defined as the combination 'positive U/S' and/or 'positive AMH' (n = 639) than by either only U/S-only (standard definition, n = 612) or by AMH-only (n = 601). With this combination, PCOM was recognized in 637 of the 639 cases that met the Rotterdam classification, and phenotype B practically disappeared. In this population, U/S and AMH markers were discordant for PCOM in 103 (16.1%) cases (9% U/S-only, 7.1% AMH-only, P = 0.159). The markers used had no other significant impact on the phenotypic distribution (except for phenotype B). However, the percentage of cases positive by U/S-only was significantly higher in phenotype D than in phenotype A (14.1% vs. 5.8%, P < 0.05). Furthermore, in the discordant cases, plasma LH levels were significantly higher in the AMH-only group than in the concordant cases, and fasting insulin serum levels tended to be higher in the U/S-only group. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study. A referral bias explains the relatively high proportion of patients with phenotype D (28%). PCOM was defined by in-house thresholds. The AMH assay used is no longer commercially available. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that ideally both U/S data and serum AMH level should be integrated to define PCOM in the Rotterdam classification. In a cost-effectiveness approach, the choice of one or the other has little impact on the diagnosis and the phenotyping of PCOS. STUDY FUNDING/COMPETING INTEREST(S): No external funding. The authors have no conflict of interest to declare.

Effect of obesity and its related metabolic factors on serum anti-Müllerian hormone concentrations in women with and without polycystic ovaries.

The relationship between serum anti-Müllerian hormone (AMH) levels, body mass index (BMI) and related metabolic factors were investigated in women with polycystic ovary syndrome (PCOS). A total of 691 women aged between 18 and 35 years, referred to the Department of Gynaecological Endocrinology at the University Hospital of Lille between 2009 and 2014 were included: 137 controls and 554 women with PCOS. Mean serum AMH levels were slightly but significantly lower in women with PCOS who were overweight or obese (BMI ≥25) compared with women of normal weight (BMI <25) (P < 0.05). No such difference was found in the control group. After bivariate analysis, no significant correlation was found between BMI and AMH in controls. In the PCOS group, this relationship was significant (P = 0.0001) but weak (r = -0.177). Stepwise multiple regression analysis yielded a significant model, including five variables (follicle count, serum androstenedione, BMI, serum LH and FSH) explaining 38.6%, 3.4%, 1.4%, 0.7% and 1.4% of the total serum AMH variance, respectively. No effect of metabolic status was found on serum AMH levels in controls, but a significant, albeit weak, negative independent correlation was found between AMH and BMI in women with PCOS.

Blepharophimosis, short humeri, developmental delay and hirschsprung disease: expanding the phenotypic spectrum of MED12 mutations.

We report on two male sibs, a fetus and a newborn, with short humeri and dysmorphic facial features including blepharophimosis. The newborn also had Hirschsprung disease. Goldberg-Shprintzen syndrome and the Say-Barber-Biesecker-Young-Simpson type of Ohdo syndrome were suspected but direct sequencing of KBP and KAT6B failed to identify a mutation. Finally, direct sequencing of MED12, the gene mutated in Opitz-Kaveggia syndrome, Lujan-Fryns syndrome and X-linked Ohdo syndrome identified in the two sibs the missense mutation c.3443G>A (p.Arg1148His) inherited from the mother. This report further expands the phenotypic spectrum of MED12 mutations.

A comprehensive multiplatform metabolomic analysis reveals alterations of 2-hydroxybutyric acid among women with deep endometriosis related to the pesticide trans-nonachlor.

BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.

[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

Palmo-Plantar hyperkeratosis, intellectual disability, and spastic paraplegia in two maternal half brothers: further evidence for an X-linked inheritance.

In 1983, Fitzsimmons et al. reported four brothers with an unrecognized disorder characterized by intellectual disability, spastic paraplegia, and palmo-plantar hyperkeratosis (OMIM 309500). In this report, we describe a family in which two males, maternal half-brothers, had learning disabilities. Both patients also showed spasticity in the lower limbs and palmo-plantar hyperkeratosis. The mother of the affected boys had learning difficulties but did not show any dermatological symptoms. This report confirms that the association of features reported by Fitzsimmons et al. is a distinct entity and further suggests an X-linked mode of inheritance.

Assisted reproductive techniques do not impact late neurodevelopmental outcomes of preterm children.

Objective: Assisted reproductive technology (ART) increases the rate of preterm births, though few studies have analyzed outcomes for these infants. No data are available on 4-year-old children born prematurely after ART. The objective was to investigate whether ART affect the neurodevelopmental outcomes at 4 years in preterm infants born before 34 weeks of gestational age (GA). Methods and results: A total of 166 ART and 679 naturally conceived preterm infants born before 34 weeks GA between 2013 and 2015 enrolled in the Loire Infant Follow-up Team were included. Neurodevelopment was assessed at 4 years using the age and stage questionnaire (ASQ) and the need for therapy services. The association between the socio-economic and perinatal characteristics and non-optimal neurodevelopment at 4 years was estimated. After adjustment, the ART preterm group remained significantly associated with a lower risk of having at least two domains in difficulty at ASQ: adjusted odds ratio (aOR) 0.34, 95% confidence interval (CI) (0.13-0.88), p = 0.027. The factors independently associated with non-optimal neurodevelopment at 4 years were male gender, low socio-economic level, and 25-30 weeks of GA at birth. The need for therapy services was similar between groups (p = 0.079). The long-term neurodevelopmental outcomes of preterm children born after ART are very similar, or even better than that of the spontaneously conceived children.

Impact of the duration of oestradiol treatment on live birth rate in Hormonal Replacement Therapy cycle before frozen blastocyst transfer.

Although the duration of progesterone administration in Hormonal Replacement Therapy (HRT) cycles before frozen embryo transfer is standardized, the optimal duration of oestrogen treatment remains controversial. In this monocentric retrospective study conducted in all single frozen blastocyst transfer (FBT) performed with HRT between January 2016 and July 2019, we evaluated the association between the duration of oestradiol treatment before FBT and live birth rate (LBR) in HRT cycles. Cycles were gathered in 3 groups according to quartiles of duration of oestrogen treatment. LBR was compared across the 3 groups and multivariate analysis was performed. We included 2235 single FBT cycles; 507, 1257 and 471 with E2 treatment below 23 days, 23-30 days (reference) and more than 30 days respectively. After multivariate analysis and adjustment, no significant difference in LBR was found between below 23 or more than 30 days and reference groups (OR = 0.93 [0.68-1.27] and OR = 1.29 [0.88-1.89] respectively). Complementary sensitivity analysis led to a non-significant adjusted OR = 1.66 [IC 0.9-3.1]. In conclusion, our study showed that the duration of E2 treatment in HRT cycles before FBT is not associated with LBR.

What is the best strategy for slowly developing blastocysts?

Day 5 fresh blastocyst transfers results in higher clinical pregnancy and live birth rates than day 6 fresh blastocyst transfer. This study aimed to identify the strategy to adopt with slowly developing blastocysts. Should not fully expanded blastocyst on day 5 be transferred on day 5, or when expanded on day 6, or be frozen? 1093 single blastocyst transfer cycles performed between January 2016 and December 2018 were divided in 4 groups: day 5 fresh transfers of full or expanded blastocyst (≥B3), day 5 fresh transfers of slowly developing blastocysts (B1 or B2), day 6 fresh transfers of expanded blastocysts (≥B4), day 6 frozen-thawed single blastocyst transfer cycles. Clinical pregnancy rate and live birth rate were significantly higher with fresh expanded blastocyst transfer on day 5 than in any other group. No statistical difference could be found between the other 3 groups. Slowly developing day 5 blastocysts have poorer implantation potential than expanded day 5 blastocysts but can be fresh transferred on day 5 rather than being cultured until day 6 for transfer or freezing when no expanded blastocyst is available on day 5.

Should artificial shrinkage be performed prior to blastocyst vitrification? A systematic review of the literature and meta-analysis.

Embryo vitrification is increasingly used in IVF. Artificial shrinkage (collapse) before vitrification has been proposed to maximise blastocyst survival after warming. However, its effectiveness on blastocyst survival rate and vitrified-warmed blastocyst transfer cycle outcome remains to be confirmed. Therefore, we performed a systematic MEDLINE search according to PRISMA guidelines on all articles published up to April 2018 and related to human blastocyst collapse before vitrification using the following keywords: (i) blastocyst; (ii) collapse; (iii) artificial shrinkage; and (iv) vitrification. The following outcomes were analysed and included in the meta-analysis: (i) blastocyst survival rate after warming; (ii) implantation rate; (iii) clinical pregnancy rate; and (iv) live birth rate after vitrified-warmed blastocyst transfer (commonly named frozen-thawed blastocyst transfer). Eight articles were included. Briefly, blastocyst survival (OR 5.04, 95% CI 2.43-10.46) and clinical pregnancy rate (OR 1.87, 95% CI 1.26-2.77) were significantly higher in collapse than in control group. However, implantation rate (OR 2.50, 95% CI 0.67-9.28) and live birth rate (OR 1.35, 95% CI 0.88-2.09) were comparable in both groups. In conclusion, this systematic review and meta-analysis suggests that artificial shrinkage before blastocyst vitrification improves survival and clinical pregnancy rate, but not implantation or live birth rate. Further randomised studies are warranted to improve the level of evidence and confirm these findings.

Kaolin consumption in pregnant women: what impact on the weight of newborns?

BACKGROUND: Geophagy is an ancestral practice particularly found among African women who describe beneficial effects on the sympathetic signs of pregnancy. Studies have reported a significant prevalence of consumption of kaolin, known as geophagy, within migrant population. However, this behavior, like other environmental factors, could lead to obstetrical and neonatal risks. OBJECTIVE: The objective of our study was to evaluate the obstetrical and neonatal impact of kaolin consumption, especially on Z-SCORE for weight-for-gestational age in the newborn. METHODS: This mono-centric historical cohort study was carried out on the basis of questionnaires and patients' obstetrical records. It was conducted between January 1 and July 1, 2017. Patients were divided into two groups: 1) women who consumed kaolin (at least once during their pregnancy), and 2) women who did not consume kaolin. Morphometric characteristics of the newborn were retrieved in obstetrical records. RESULTS: Results: 105 pregnant women were included: 26 exposed and 79 non exposed. Women who consumed kaolin were more frequently without social protection at their first consultation (p < .01). Multivariate analysis did not show a significant association between Z-SCORE for weight-for gestational age in the newborn and kaolin consumption (ß = 0.13, p = .54) after adjusting on age, precariousness, BMI, intake of toxic substances, anemia and beginning eclampsia. Among these covariates, precariousness was significantly associated with both a decrease in Z-SCORE for weight (ß = -0.87, p < .002) and size (ß = -0.68, p < .01). CONCLUSION: Geophagy is not to be neglected in socially advantaged countries due to increased immigration. This study found no association between kaolin consumption and birth weight. However, there was a correlation between precariousness and low birth weight which reinforces the importance of tightening the follow-up during pregnancies in the most precarious women.

Is low anti-Mullerian hormone (AMH) level a risk factor of miscarriage in women <37 years old undergoing in vitro fertilization (IVF)?

Anti-Mullerian Hormone (AMH) is considered to be one of the most relevant markers of ovarian reserve. However, its association with oocyte quality, pregnancy occurrence and evolution remain to be further investigated. The objective of this study was to compare miscarriage rate after fresh blastocyst(s) transfer in young women (<37 years old) with or without diminished ovarian reserve (DOR), as reflected by low serum AMH levels. This monocentric retrospective study was conducted in 669 women undergoing 1,891 blastocyst transfers. Patients were divided into 2 groups: (1) 190 transfers performed in 106 women with a 'low' serum AMH (< 10th percentile) (i.e. AMH < 0.85 ng/mL); and (2) 961 transfers performed in 563 patients with a 'normal' serum AMH (25th-75th percentile) (i.e. AMH 1.4-4 ng/mL). Miscarriage rate was comparable in both groups (9.5 and 6.8% respectively; p = 0.2) as well as implantation rate, pregnancy rate, live birth rate per transfer (p = 0.4, p = 0.07 and p = 0.6, respectively). After multivariate analysis, no significant association was found between serum AMH level and miscarriage rate (p = 0.22). In women <37 years, low serum AMH level is not associated with an increase in miscarriage rate after fresh blastocyst transfer.