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RESEARCH QUESTION : What is the discontinuation rate among patients with remaining cryopreserved embryos in Belgium and what are the reasons for discontinuation? DESIGN : Multicenter, cross-sectional study performed in 11 Belgian fertility clinics (covering 80% of ART population). Patients were eligible (n=1917) in case they underwent an unsuccessful fresh embryo transfer (fresh group) or FET (in between group) and did not start a subsequent FET cycle within one year despite the presence of remaining cryopreserved embryos. Denominator were all patients with embryos cryopreserved during the same period (2012-2017) (n=21329). Data were collected through an online anonymous questionnaire. RESULTS : The discontinuation rate for patients with remaining cryopreserved embryos is 9% (1917/21329). For the final analysis, 304 completed questionnaires were included. The most important checked reasons for discontinuation of FET cycles were psychological (50%) and physical (43%) burden, impact on work (29%), woman's age (25%) and impact on relationship (25%). In 69% of the cases the patient her/himself made the decision to delay FET treatment. In 16% of the respondents, the decision to delay FET was determined by external factors: treating physician (9%), social environment (4%), close family (3%) and society (3%). Suggested improvements by the respondents were psychological support before (41%), during (51%) and after (51%) treatment, as well as lifestyle counseling (44%) and receiving digital information (43%). CONCLUSIONS : The discontinuation rate is remarkably high in patients with remaining cryopreserved embryos, who are considered to have a good prognosis. Respondents stressed the need to better integrate psychological and patient tailored care in our daily ART practice.

RESEARCH QUESTION: How do cumulative live birth rates (CLBR), cumulative multiple live birth rates (CMLBR) and dropout rates over six IVF and intracytoplasmic sperm injection (ICSI) cycles change over time? DESIGN: Prospective longitudinal cohort (n = 16,073 patients; 48,946 cycles) starting a first fresh assisted reproductive technology cycle between 1 January 2014 and 31 December 2016, with follow-up until 31 December 2017. Outcomes between the periods 2014-2017 and 2009-2012 were compared. RESULTS: Conservative estimates of CLBR after six complete cycles were significantly higher in women younger than 35 years after every cycle: one to three, adjusted P-value [p adj] < 0.0001; four, p = 0.01; five, p adj = 0.03; six, p adj = 0.04) and after the first cycle in women aged 35-37 years (p adj = 0.04) in 2014-2017 versus 2009-2012. For an optimal estimate, the CLBR was significantly higher after the first three cycles in women younger than 35 years (all p adj < 0.0001) and after the first cycle in women aged 35-37 years (p adj = 0.04). The CMLBR rate decreased from 5.1% ± 0.19 (SE) to 4.1% ± 0.16 for the conservative estimate and from 8.6% ±0.37 (SE) to 6.7% ± 0.30 for the optimal estimate after six complete cycles for the whole cohort. Dropout rates of complete cycles were 26.5% 29.4%, 33.4%, 38.9% and 47.3% after the first to fifth cycle, respectively. Compared with 2009-2012, the dropout rate in the current period was significantly higher for the first (P < 0.0001) and second (P = 0.0124) cycle. CONCLUSION: Over six complete IVF/ICSI cycles, CLBR and dropout rates increased and multiple live birth rates decreased when 2014-2017 was compared with 2009-2012. ispartof: REPRODUCTIVE BIOMEDICINE ONLINE vol:42 issue:4 pages:717-724 ispartof: location:Netherlands status: published

Study question Can SARS-CoV-2 mRNA be detected in the reproductive tract of asymptomatic patients undergoing ART? Summary answer SARS-CoV-2 mRNA is not detectable in semen, follicular fluid, vaginal secretions or residual medulla from ovarian tissue cryopreservation procedures in asymptomatic patients who undergo ART, irrespective of the results of a triage questionnaire and a nasopharyngeal SARS-CoV-2 RNA detection test. What is known already The SARS-CoV-2 pandemic had a huge impact on the activities of fertility clinics. Although some studies reported the presence of SARS-CoV-2 mRNA in the reproductive system during or after acute COVID-19 symptomatic infections, uncertainties remain regarding the presence of viral mRNA in the reproductive material and follicular fluid of asymptomatic patients undergoing ART. Study design, size, duration An observational cohort trial of residual material samples including semen, follicular fluid, vaginal secretions and ovarian medulla was conducted during the second pandemic wave in Brussels, from September, 2020 to April, 2021. Participants/materials, setting, methods All patients who underwent ART (IIU, IVF/ICSI, oocyte and ovarian tissue cryopreservation) responded to a triage questionnaire at the beginning and end of the cycle and underwent nasopharyngeal swab collection for SARS-CoV-2 RNA detection by RT-PCR before the procedure according to standard recommendations. For semen analysis, only the questionnaire was requested the day before the sample collection. The ART cycles of patients with positive nasopharyngeal SARS-CoV-2 RNA detection tests and/or questionnaires were canceled except for those that could not be postponed. After providing informed consent, swabs on residual materials were collected the day of the oocyte, ovarian tissue or semen collection and were processed for RT-qPCR. Main results and the role of chance A total of 394 samples from 291 patients were analysed. Amongst them, 20 samples were obtained from patients with a positive questionnaire but negative nasopharyngeal SARS-CoV-2 test and 20 others were from patients with a positive nasopharyngeal SARS-CoV-2 test. The remaining samples were collected from patients with a negative or unknown nasopharyngeal SARS-CoV-2 test and/or a negative or unknown triage questionnaire. Viral RNA for SARS-CoV-2 was undetectable in all of the samples. Limitations, reasons for caution Considering the cancellation policy, only a limited number of samples from patients with positive triage questionnaires or nasopharyngeal SARS-CoV-2 tests were included in the analysis. Wider implications of the findings The study suggested that there was no risk of reproductive tract contamination by SARS-CoV-2 in asymptomatic patients, irrespective of the results from a triage questionnaire or nasopharyngeal SARS-CoV-2 test. The results suggested that no additional measures to prevent staff or cross-patient contamination need to be implemented in the IVF and andrology laboratories. Study funding/competing interest(s) This study was funded by Université Libre de Bruxelles and by a grant from Ferring. AD and ID received a grant from Ferring for the study. The authors have no other conflict of interest to declare related to this study., info:eu-repo/semantics/published

We report on the results of array-CGH and Whole exome sequencing (WES) studies carried out in a Tunisian family with 46,XX premature ovarian insufficiency (POI). This study has led to the identification of a familial Xp22.12 tandem duplication with a size of 559.4 kb, encompassing only three OMIM genes (RPS6KA3, SH3KBP1and EIF1AX), and a new heterozygous variant in SPIDR gene: NM_001080394.3:c.1845_1853delTATAATTGA (p.Ile616_Asp618del) segregating with POI. Increased mRNA expression levels were detected for SH3KBP1 and EIF1AX, while a normal transcript level for RPS6KA3 was detected in the three affected family members, explaining the absence of intellectual disability (ID). To the best of our knowledge, this is the first duplication involving the Xp22.12 region, reported in a family without ID, but rather with secondary amenorrhea (SA) and female infertility. As EIF1AX is a regulatory gene escaping X-inactivation, which has an extreme dosage sensitivity and highly expressed in the ovary, we suggest that this gene might be a candidate gene for ovarian function. Homozygous nonsense pathogenic variants of SPIDR gene have been reported in familial cases in POI. It has been suggested that chromosomal instability associated with SPIDR molecular defects supports the role of SPIDR protein in double-stranded DNA damage repair in vivo in humans and its causal role in POI. In this family, the variant (p.Ile616_Asp618del), present in a heterozygous state, is located in the domain that interacts with BLM and might disrupt the BLM binding ability of SPIDR protein. These findings strengthen the hypothesis that the additional effect of this variant could lead to POI in this family. Although the work represents the first evidence that EIF1AX duplication might be responsible for POI through its over-expression, further functional studies are needed to clarify and prove EIF1AX involvement in POI phenotype.

Purpose Ovarian stimulation for oocyte and embryo cryopreservation is the standard of care for fertility preservation in young breast cancer patients before gonadotoxic chemotherapy. The procedure should be started as soon as possible to avoid delay of treatment; thus, it is often performed concomitantly with tumor staging assessments. However, questions remain regarding the potential negative impact on oocyte quality that may occur due to exposure to scattered ionizing radiation from imaging techniques when staging assessment is conducted at the same time as ovarian stimulation. Methods We conducted a retrospective study on all breast cancer patients who received ovarian stimulation for fertility preservation at our center between November, 2012 and May, 2020. Results Gynecologic and oncologic characteristics were similar between patients exposed (n = 14) or not (n = 60) to ionizing radiation. Exposed patients started the ovarian stimulation sooner after diagnosis than non-exposed patients (11.5 vs 28 days, respectively, P

What is the functional relevance of decreased pulmonary vascular distensibility in adolescents conceived by IVF?, info:eu-repo/semantics/published

Study question Is SARS-CoV–2 detected by RT-PCR in the reproductive materials and follicular fluid of asymptomatic patients undergoing fertility treatments? Summary answer No SARS-CoV–2 mRNA was detected in sperm, vaginal and follicular fluids samples of asymptomatic patients, irrespective of the nasopharyngeal swab or COVID–19 questionnaire results. What is known already: The COVID–19 pandemic had a huge impact on health care including on fertility clinics. While activities were interrupted during the first wave, ART cycles are currently performed but uncertainties remain regarding the presence of the virus in reproductive materials. The SARS-CoV–2 receptors were detected in reproductive organs but only few studies with limited number of cases reported the presence of SARS-CoV–2mRNA in semen of symptomatic patients. In women, the risk of SARS-CoV–2 contamination in follicular and vaginal fluids remains uncertain. Thus the risk of sexual transmission and the safety of the IVF laboratory procedures are unclear. Study design, size, duration This COVART study is an observational cohort prospective trial conducted at a Belgian academic hospital. Between September 2020 and January 2021, 208 asymptomatic adults patients (men and women) undergoing ART treatments (sperm analysis, IUI, ICSI/ICF cycles, oocyte cryopreservation) were included in the trial after informed consent. All patients followed standard procedures to evaluate COVID–19 risk (nasopharyngeal swab during ovarian stimulation and COVID–19 risk questionnaire). Participants were divided into two groups: COVID–19 positive and negative/unknown groups. Participants/materials, setting, methods: Swabs on the residual reproductive materials were done and stored in viral transport medium at 4 °C until processing. After addition of an internal control in each sample and virus inactivation with Trizol, mRNA was extracted using phenol-chloroform method. Quantitative RT-PCR was performed in duplicate following a previously validated protocol (45 cycles, Roche Light Cycler 480). Negative/positive controls were used to validate each run. The test was considered as positive when CT Main results and the role of chance A total of 399 samples (126 semen, 162 vaginal fluid, 111 follicular fluid samples) of reproductive residual materials from 208 participants were collected during the peak of the second wave of COVID–19 pandemic, when Belgium was considered as a red zone with a viral Rt of 1.516 and a 14-day COVID–19 cases notification rate above 630 per 100000. Although the policy of the fertility clinic was to cancel all cycles of patients with a positive nasopharyngeal swab test except if specific medical raisons to continue the cycle, 14 samples from 9 non-cancelled patients diagnosed with COVID–19 before or just after the samples collection were analyzed (4 sperm, 5 follicular fluid and 5 vaginal secretion samples). For the 199 remaining patients, the COVID–19 status was negative or unknown. None of the samples were considered as positive after quantitative RT-PCR analysis. Limitations, reasons for caution All the patients were asymptomatic at the time of the samples collection and the large majority was negatively diagnosed for COVID–19 during the ART cycle. The results should be confirmed by including a larger cohort of positive patients. Data on the impact on ART outcomes will be evaluated. Wider implications of the findings: We showed that contaminations of sperm, follicular and vaginal fluids with SARS-CoV–2 are unlikely in asymptomatic patients, even when diagnosed positive, confirming the poor risk of sexual transmission. Moreover, no additional safety measures seems to be implemented in the IVF laboratory to ensure the safety of the staff. Trial registration number P2020/414

Study question Is Anti-Müllerian hormone (AMH) level associated with the probability of obtaining an ongoing pregnancy (OP) and with time to pregnancy (TTP) in women undergoing d-IUI? Summary answer AMH is neither associated with the probability of obtaining an OP nor with time to pregnancy (TTP) in women undergoing d-IUI What is known already Anti-Müllerian hormone (AMH) is a glycoprotein produced by the granulosa cells of preantral and antral follicles. While AMH has been widely recognized as a quantitative marker of ovarian reserve used to predict ovarian responsiveness to ovarian stimulation in IVF, its relationship with fecundability in spontaneous conceptions is still a matter of debate. There is currently no consensus on the role of AMH on time to pregnancy in unassisted conceptions. The question of whether AMH is a qualitative marker of oocyte quality is therefore still unanswered. Study design, size, duration This prospective cohort study was carried out between 9/1/2017 and 12/30/2020 on 592 women aged 19 to 44, who underwent d-IUI in a natural cycle (n = 1788) the day after LH peak. Patients were single, homosexual, or heterosexual with an infertile partner and underwent 1 to maximum 6 d-IUI. All patients had regular ovulatory cycles and bilateral tubal patency confirmed before starting d-IUI. AMH evaluation was performed within the previous 3 months of the first d-IUI. Participants/materials, setting, methods The primary outcomes were the likelihood of obtaining an OP (>14 weeks) and TTP calculated as the number of d-IIU up to an OP. Multivariate logistic regression was used to compare the probability of obtaining an OP according to age and AMH levels. Kaplan-Meier curves with log-rank test were used to assess the TTP stratified by age groups (≤35, >35 to ≤ 39, and > 39 years old) and AMH groups (< 1ng/mL and ≥ 1ng/mL). Main results and the role of chance AMH levels were negatively correlated with age (p 35 to ≤ 39 years old (n = 136) and > 39 years old (n = 118) (p Limitations, reasons for caution Our results concern d-IUI and can therefore not be extrapolated to natural conception. However, the study model is close to natural fecundity as there was no history of female infertility and as all IUI were performed on the day of ovulation with donor sperm proven to be fertile. Wider implications of the findings: While measuring AMH seems necessary for gonadotropin dose adjustment in ART, our data suggest that it cannot qualitatively assess fertility outcome and should therefore not be used routinely for preconception counseling in the absence of infertility history. Trial registration number P2017/396

STUDY QUESTION What is the risk of recurrence in young breast cancer survivors who undergo ARTs following completion of anticancer treatment? SUMMARY ANSWER ART in breast cancer survivors does not appear to have a negative impact on disease-free survival. WHAT IS KNOWN ALREADY In healthy women, fertility treatment does not increase the risk of developing breast cancer. At the time of breast cancer diagnosis and before starting anticancer treatments, several studies have shown the safety of performing ART. However, the safety of ART in breast cancer survivors following completion of anticancer treatment remains under-investigated. In general, breast cancer survivors are counselled to avoid any hormonal treatment but there are limited data available on the effect of short exposure to high oestradiol levels during ART. The largest study in this regard included 25 breast cancer survivors exposed to ART and did not show a detrimental effect of ART on patient survival. Hence, taking into account that pregnancy after breast cancer does not affect cancer prognosis, defining the safety of ART in breast cancer survivors remains a priority. STUDY DESIGN, SIZE, DURATION We conducted a retrospective multicentric matched cohort study including a cohort of breast cancer survivors who underwent ART (exposed patients) between January 2006 and December 2016. Exposed patients who were eligible for the study were matched according to known breast cancer prognostic factors. Matched breast cancer survivors did not undergo ART (non-exposed patients) and were disease-free for a minimum time that was not less than the time elapsed between breast cancer diagnosis and first ART for the matched ART-exposed patients. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were retrieved from all survivors who had been diagnosed with breast cancer in eight participating centres at an age of ≤40 years, without metastasis, ongoing pregnancy, pre-existing neoplasia or ovarian failure. ART included ovarian stimulation for IVF/ICSI, clomiphene citrate treatment and hormone replacement therapy for embryo transfer. Data were collected from an oncological database for the selection of breast cancer patients in the non-exposed group. Exposed patients were matched (1:2) for germline BRCA status, tumour stage, anticancer treatment and age, whenever feasible. Matched groups were compared at baseline according to characteristics using conditional logistic regression. Kaplan–Meier curves were constructed to compare time to recurrence between groups, with the time of ART as starting point that has been adjusted in the non-exposed group. The analyses were performed using Stata IC/15.1. MAIN RESULTS AND THE ROLE OF CHANCE A total of 39 breast cancer patients in the ART group were eligible for the analysis and were matched with 73 controls. There was no statistical difference between the two groups for the presence of BRCA mutation, tumour characteristics, use of (neo)adjuvant chemotherapy and of adjuvant endocrine therapy. Exposed patients were younger than non-exposed patients (mean age 31.8 vs 34.3 years, respectively; P, info:eu-repo/semantics/published

To assess the birthweight of neonates conceived after fresh and frozen embryo transfers (FET) and, if different, to investigate whether estradiol levels during the late follicular phase were associated with the observed difference.Singleton pregnancies from fresh and FET transfers between January 1990 and December 2013 were compared retrospectively. A total of 2885 singleton pregnancies after fresh embryo transfer and 746 after FET were analyzed. Obstetric and neonatal outcomes were compared between fresh and FET cycles.The singletons born after FET were found to have a significantly higher birth weight (3313 g), compared to those born after fresh embryo transfer (3143 g); p .001. The main predictor of this difference was found to be estradiol levels at the end of the follicular phase. The difference in birthweight was inversely correlated to estradiol levels considering all cycles together but also considering fresh and frozen cycles separately.Our study demonstrates a link between high estradiol levels and low birth weight of singletons after IVF both in fresh and frozen-thawed embryo transfer cycles. It provides additional support to the involvement of hyperestrogenemia in the process of implantation and on the subsequent fetal development.

Background: Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality. Methods: In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups. Results: FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4-438) vs 64.4 (43.8-152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5-466.7) vs 354 (179-511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa. Conclusions: Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients. Trial registration: Clinicaltrials.gov - NCT02661932, registered 25 January 2016, retrospectively registered., SCOPUS: ar.j, info:eu-repo/semantics/published

Objective: To find the genetic etiology of premature ovarian insufficiency (POI) in a patient with primary amenorrhea and hypergonadotropic hypogonadism. Design: Case report. Setting: University hospital. Patient(s): A Belgian woman aged 32 years with POI at the age of 17, her parents, and her sister whose POI was diagnosed at age 29. Intervention(s): Analysis of a panel of 31 genes implicated in POI (POIGP) using next-generation sequencing (NGS), Sanger sequencing, and in vitro functional study. Main Outcome Measure(s): Gene variants, family mutational segregation, and in vitro functional impact of the mutant proteins. Result(s): The analysis of the gene panel using NGS identified the presence of two novel follicle-stimulating hormone receptor (FSHR) missense mutations at a compound heterozygous state in the affected patient: c.646 G>A, p.Gly216Arg, and c.1313C>T, p.Thr438Ile. Sanger sequencing showed the presence of each mutation at heterozygous state in the patient's parents and at heterozygous compound state in the affected sister. Both substituted amino acids (Gly216 and Thr438) were conserved in FSHR of several vertebrate species as well as in other glycoproteins receptors (TSHR and LHCGHR), suggesting a potentially important role in glycoprotein receptor function. An in vitro functional study showed similar results for both variants with more than 90% reduction of their cell surface expression and a 55% reduction of their FSH-induced cyclic adenosine 3′:5′ monophosphate (cAMP) production compared with the wild-type FSHR. Conclusion(s): The analysis of a gene panel of 31 genes implicated in POI allowed us to identify two novel partially inactivating mutations of FSHR that are likely responsible for the POI phenotype of the proband and of her affected sister., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Preclinical evidence suggests a possible negative impact of deleterious BRCA mutations on female fertility. However, limited and rather conflicting clinical data are available. This study assessed the reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients. Patients and methods This was a retrospective analysis of two prospective studies investigating oocyte cryopreservation and ovarian tissue cryopreservation in newly diagnosed early breast cancer patients. In the current analysis, baseline anti-Mullerian hormone (AMH) and performance of cryopreservation strategies were compared between patients with or without germline deleterious BRCA mutations. Results Out of 156 patients included, 101 had known BRCA status of whom 29 (18.6%) were BRCA-mutated and 72 (46.1%) had no mutation. Median age in the entire cohort was 31 years [interquartile range (IQR) 28–33). Median AMH levels were 1.8 µg/l (IQR 1.0–2.7) and 2.6 µg/l (IQR 1.5–4.1) in the BRCA-positive and BRCA-negative cohorts, respectively (P = 0.109). Among patients who underwent oocyte cryopreservation (N = 29), women in the BRCA-positive cohort tended to retrieve (6.5 versus 9; P = 0.145) and to cryopreserve (3.5 versus 6; P = 0.121) less oocytes than those in the BRCA-negative cohort. Poor response rate (i.e. retrieval of ≤4 oocytes) was 40.0% and 11.1% in the BRCA-positive and BRCA-negative cohorts, respectively (P = 0.147). Among patients who underwent ovarian tissue cryopreservation (N = 72), women in the BRCA-positive cohort tended to have a numerically lower number of oocytes per fragment (0.08 versus 0.14; P = 0.193) and per square millimeter (0.33 versus 0.78; P = 0.153) than those in the BRCA-negative cohort. Two BRCA-mutated patients were transplanted after chemotherapy and one delivered at term a healthy baby. No difference between BRCA1- and BRCA2-mutated patients was observed in any of the above-mentioned outcomes. Conclusion A consistent trend for reduced reproductive potential and performance of cryopreservation strategies was observed in BRCA-mutated breast cancer patients. Independent validation of these results is needed.

The aim of this study was to evaluate whether pregnancies resulting from oocyte donation have a higher risk of preeclampsia compared with pregnancies after IVF using autologous oocytes. Propensity score matching on maternal age and parity was carried out on a one to one basis, and a total of 144 singleton pregnancies resulting in delivery beyond 22 gestational weeks, achieved by oocyte donation, were compared with 144 pregnancies achieved through IVF and intracytoplasmic sperm injection with the use of autologous oocytes. All pregnancies were achieved after fresh embryo transfer. Obstetric and neonatal outcomes were compared for each pregnancy. Singleton pregnancies after oocyte donation were associated with a significantly higher risk for preeclampsia (OR 2.4, CI 1.02 to 5.8; P = 0.046), as well as for pregnancy-induced hypertension (OR 5.3, CI 1.1 to 25.2; P = 0.036), and caesarean delivery (OR 2.3, CI 1.4 to 3.7; P = 0.001) compared with pregnancies using autologous oocytes.

Gonadotropins have been available for clinical use for > 60 years for many conditions in the field of reproductive medicine. The article provides an overview of the pioneering work leading to the wide range of pharmaceutical gonadotropin preparations currently available. It underlines the major difference between ovulation induction intended to restore normal ovulation and promote monofollicular development in anovulatory patients and controlled ovarian hyperstimulation intended to induce a multi-follicular ovulation in infertile patients, often ovulatory, in order to increase their chance of conception. Different treatment regimens are addressed that are intended to avoid major side-effects, such as high-order multiple pregnancies and OHSS.

Sex differences are observed in the evolution of numerous inflammatory conditions. Women exhibit better clinical courses compared to men in acute inflammatory processes, yet worse prognosis in several chronic inflammatory diseases. Inflammatory markers are significantly different between prepubertal boys and girls, whose sex steroid levels are very low, suggesting genetics play a role. To evaluate the potential influence of the X chromosome, we studied cytokine production and protein phosphorylation following Toll-like receptor (TLR) activation in whole blood and purified neutrophils and monocytes of healthy adults of both sexes as well as subjects with Klinefelter syndrome. We recorded higher levels of inflammatory cytokines in men compared to both women and patients with Klinefelter syndrome following whole blood stimulation. In purified monocytes, production of inflammatory cytokines was also higher in men compared to women, while Klinefelter subjects expressed the same pattern of cytokine production as males, in contrast with whole blood analyses. These differences remained after adjusting for sex steroid levels. Our study revealed higher cytokine inflammatory responses in men than women, yet also compared to subjects with Klinefelter syndrome, who carry two copies of the X chromosome, like women, and thus potentially benefit from the cellular mosaicism of X-linked genes., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. OBJECTIVE In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. DESIGN Controlled, randomised, prospective, double-blinded study. SETTING The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. PATIENTS Of the 132 women undergoing oocyte retrieval included, 121 completed the study. INTERVENTION After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. MAIN OUTCOME MEASURES The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. RESULTS No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation

The purpose of the present study is to study what is the best predictor of severe ovarian hyperstimulation syndrome (OHSS) in IVF. This is a retrospective analysis of all consecutive IVF/intracytoplasmic injection cycles performed during a 5-year period (2009–2014) in a single university fertility centre. All fresh IVF cycles where ovarian stimulation was performed with gonadotrophins and GnRH agonists or antagonists and triggering of final oocyte maturation was induced with the administration of urinary or recombinant hCG were analyzed (2982 patients undergoing 5493 cycles). Because some patients contributed more than one cycle, the analysis of the data was performed with the use of generalized estimating equation (GEE). Severe OHSS was diagnosed in 20 cycles (0.36%, 95% CI 0.20–0.52). The number of follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles. The cutoff in the number of follicles ≥10 mm with the best capacity to discriminate between women that will and will not develop severe OHSS was ≥15. The presence of more than 15 follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles.

Ovarian insufficiency is a major long-term adverse event, following the administration of a myeloablative conditioning regimen, and occurring in >80% of children and adolescents receiving such treatment for malignant or non-malignant disease. Cryopreservation of ovarian tissue is currently offered to preserve the fertility of these young patients. At least 35 live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age. We report here the first live birth after autograft of cryopreserved ovarian tissue in a woman with primary ovarian failure after a myeloablative conditioning regimen as part of a hematopoietic stem cell transplantation performed for homozygous sickle-cell anemia at age 14 years. This first report of successful fertility restoration after the graft of ovarian tissue cryopreserved before menarche offers reassuring evidence for the feasibility of the procedure when performed during childhood.

Ovarian insufficiency is a major long-term adverse event, following the administration of a myeloablative conditioning regimen, and occurring in80% of children and adolescents receiving such treatment for malignant or non-malignant disease. Cryopreservation of ovarian tissue is currently offered to preserve the fertility of these young patients. At least 35 live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age. We report here the first live birth after autograft of cryopreserved ovarian tissue in a woman with primary ovarian failure after a myeloablative conditioning regimen as part of a hematopoietic stem cell transplantation performed for homozygous sickle-cell anemia at age 14 years. This first report of successful fertility restoration after the graft of ovarian tissue cryopreserved before menarche offers reassuring evidence for the feasibility of the procedure when performed during childhood.