Pollution and endometriosis: A deep dive into the environmental impacts on women's health.

BACKGROUND: The interaction between pollution and endometriosis is a pressing issue that demands immediate attention. The impact of pollution, particularly air and water pollution, or occupational hazards, on hormonal disruption and the initiation of endometriosis remains a major issue. OBJECTIVES: This narrative review aims to delve into the intricate connection between pollution and endometriosis, shedding light on how environmental factors contribute to the onset and severity of this disease and, thus, the possible public health policy implications. DISCUSSION: Endocrine-disrupting chemicals (EDCs) in pollutants dysregulate the hormonal balance, contributing to the progression of this major gynaecological disorder. Air pollution, specifically PM2.5 and PAHs, has been associated with an increased risk of endometriosis by enhancing chronic inflammation, oxidative stress, and hormonal imbalances. Chemical contaminants in water and work exposures, including heavy metals, dioxins, and PCBs, disrupt the hormonal regulation and potentially contribute to endometriosis. Mitigating the environmental impact of pollution is required to safeguard women's reproductive health. This requires a comprehensive approach involving stringent environmental regulations, sustainable practices, responsible waste management, research and innovation, public awareness, and collaboration among stakeholders. CONCLUSION: Public health policies have a major role in addressing the interaction between pollution and endometriosis in a long-term commitment.

Monkeypox Virus Infection in 18-Year-Old Woman after Sexual Intercourse, France, September 2022.

A monkeypox virus outbreak has spread worldwide since April 2022. We report a young woman in France positive for monkeypox virus transmitted through oral and vaginal sex. Ulceronecrotic lesions developed intravaginally and around her vulva. Health professionals should become familiar with all aspects of infection from this virus, including possible vertical transmission.

Trial of labour versus elective caesarean delivery for estimated large for gestational age foetuses after prior caesarean delivery: a multicenter retrospective study.

BACKGROUND: Lower rates of successful trial of labor after cesarean (TOLAC) in association with fetal macrosomia were previously reported. This study aimed to compare TOLAC to elective caesarean delivery (CD) in women with estimated fetal weight large for gestational age (eLGA) and a prior CD. Primary outcome was to analyse the mode of delivery in case of TOLAC. Secondary outcome was to compare maternal and foetal morbidity. METHODS: We conducted a retrospective, descriptive, multicentric, cohort study in five maternity units between January and December 2020. Inclusion criteria were: women with a single prior CD and eLGA or neonatal weight > 90th percentile with singleton pregnancy and gestational age ≥ 37 weeks. MAIN OUTCOME MEASURES: rate of vaginal delivery, maternal and fetal morbidity including: shoulder dystocia, neonatal hospitalization, fetal trauma, neonatal acidosis, uterine rupture, 3rd and 4th perineal tears, post-partum hemorrhage, and a need for blood transfusion. RESULTS: Four hundred forty women met inclusion criteria, including 235 (53.4%) eLGA. 170 (72.3%) had a TOLAC (study group) and 65 (27.7%) an elective CD (control). 117 (68.82%) TOLAC had a vaginal delivery. No significant differences were found between the two groups in the rates of: postpartum haemorrhage, transfusion, Apgar score, neonatal hospitalization, and foetal trauma. Cord lactate was higher in the case of TOLAC (3.2 vs 2.2, p < 0.001). Median fetal weight was 3815 g (3597-4085) vs. 3865 g (3659-4168): p = 0.068 in the study vs. controls group respectively. CONCLUSION: TOLAC for eLGA fetuses is legitimate because there is no difference in maternal-fetal morbidity, and the CD rate is acceptable.

The importance of on-site genetic counseling for prospective assisted reproductive technology patients.

PURPOSE: To assess the value of having an onsite genetic counseling service integrated into an assisted reproductive technology (ART) center. METHODS: Since January 2021, we have offered genetic counseling at our ART center for couples whose medical history suggests risk of transmission of a genetic disorder. The percentage of couples referred for genetic counseling, the distribution of couples according to reasons for consultation, the mode of transmission in cases of Mendelian disorders, and the frequency of mutations for those with identified genetic disorders were determined. RESULTS: In an 18-month period, 150 of 1340 couples (11.2%) enrolled for ART treatment were referred to the genetic counseling unit. Two-thirds (99/150, 66.0%) were referred for a known genetic risk, a family history of a genetic disorder or chromosomal abnormality, a serious condition of unknown cause, or consanguinity. The remaining couples had a putative genetic risk (diminished ovarian reserve, high incidence of oocyte immaturity, recurrent abortion, or severe male infertility). Of the 99 with known genetic risk, 62 (62.7%), were approved for ART treatment, 23 (23.2%) were recommended prenatal or preimplantation testing, and 14 (14.1%) were referred for further testing before undergoing ART. CONCLUSIONS: Our findings reveal great value in having an on-site genetic counseling unit for referral of ART patients. Such a unit makes the ART process smoother and safer for couples, and it lightens the burden of ART staff by removing responsibilities for which they are neither trained, nor should they have to assume.

Successful ART outcome in a woman with McCune-Albright syndrome: a case report and literature review.

McCune-Albright syndrome (MAS) is a rare genetic disease affecting multiple organs, including endocrine tissues. This endocrinopathy is sometimes responsible for infertility, as it may induce an independent functioning of the ovaries leading to anovulatory cycles. This case report describes the infertility journey of a 22-year-old female who had early puberty and irregular periods with high estrogen and progesterone levels, low FSH and LH (on day 3 of her menstrual cycle), and a multi-cystic right ovary. She received several infertility treatments: initially in vitro oocyte maturation (IVM) followed by cyst transvaginal ultrasound-guided aspiration, all unsuccessful. A right hemi-ovariectomy was performed that eventually restored regular cycles and made it possible to perform ovarian stimulation (OS) and in vitro fertilization (IVF). Live birth was obtained after the first embryo transfer.

Investigation of the reliability of semi-automatic annotation by the Geri time-lapse system.

RESEARCH QUESTION: What is the reliability of Geri® Assess 2.0 software time-lapse technology for annotating kinetic events and identifying abnormal phenotypes in preimplantation human embryos? DESIGN: Embryos were annotated using Assess 2.0 for the appearance and fading of pronuclei, and for progression to the 2-, 3-, 4-, 5- and 6-cell stages and to three blastocyst stages. Identification of reverse cleavage and direct cleavage phenotypes was also recorded. Manual annotation was undertaken after these events in a blinded fashion. Embryo scores were compared between Assess 2.0 and manual annotation. RESULTS: A total of 513 oocytes from 34 women were included. Detection rates for Assess 2.0 versus manual annotation among the 10 kinetic events and including direct cleavage and reverse cleavage ranged between 0% and 94.4%. The percentage of discordant pairs was significantly different for all 12 events analysed (P-value range 0.036 to <0.0001). The sensitivity of Assess 2.0 ranged from 68.2% to 94.4% and specificity ranged from 63.8% to 97.3%. Assess 2.0 called for verification by the embryologist for at least one event in 55.2% of oocytes assessed. Of the 297 embryos scored by manual annotation, Assess 2.0 assigned the same score for only 125 (42.1%), although after manual corrections, concordance with manual annotation scores was raised to 66.0%. CONCLUSIONS: The results reveal striking differences between Assess 2.0 and manual annotation for kinetic annotations. Failure of Assess 2.0 to detect direct cleavage events and the low detection rate of reverse cleavage are further limitations. These collective findings highlight the importance of validating time-lapse annotation software before clinical implementation. Manual verification of Assess 2.0 outputs remains essential for accurate data interpretation.

Evolving clinical challenges in uterus transplantation.

Before the first live birth following uterus transplantation (UTx) in 2014, the 1-2% of women with an absent or non-functional uterus had no hope of childbearing. With 64 cases of UTx and 34 births reported in the scientific literature, this emerging technology has the potential for translation into mainstream clinical practice. However, limitations currently include donor availability, recipient suitability, surgical challenges regarding success and complications, and recipient management after UTx and during pregnancy. This review considers these challenges and ways to overcome them so that UTx could become part of the reproductive specialist's armamentarium when counselling patients with uterine factor infertility.

Cryptic splice site poisoning and meiotic arrest caused by a homozygous frameshift mutation in RBMXL2: A case report.

Gene expression in meiotic cells in the testis is characterized by intense transcriptional activity and alternative splicing. These processes are mainly controlled by RNA-binding proteins expressed strongly in germ cells. Functional impairments in any of these proteins' functions can lead to defects in meiosis and thus severe male infertility. Here, we have identified a homozygous frameshift mutation (NM_014469.4:c.301dup; p.Ser101LysfsTer29) in the RNA-binding motif protein, X-linked like 2 (RBMXL2) gene in a man with an azoospermia due to meiotic arrest. As RBMXL2 is known to be crucial for safeguarding the meiotic transcriptome in mice testes, we hypothesized that this variant leads to cryptic splice site poisoning. To determine the variant's impact on spermatogenesis, we confirmed the absence of RBMXL2 protein in the patient's testis tissue and then evidenced abnormal expression of several spermatogenesis proteins (e.g. meiosis-specific with coiled-coil domain) known to be altered in rbmxl2 knock-out mice with meiotic arrest. Our results indicate that RBMXL2's function in spermatogenesis is conserved in mammals. We hypothesize that deleterious variant in the RBMXL2 gene can result in male infertility and complete meiotic arrest, due to the disruption of gene expression by cryptic splice site poisoning.

Endometrioma and assisted reproductive technology: a review.

PURPOSE: Endometriomas are a common cause of infertility necessitating assisted reproductive technology (ART). It had been previously thought that surgical removal of the endometriomas prior to ART would improve reproductive outcomes, but recent data suggests that surgical cystectomy might affect the ovarian reserve, decreasing the chances of ART success. The aim of this article is to review the literature on the effects of endometrioma surgery on ART outcomes providing an overview of the current evidence and assessing the need for further studies. METHODS: A literature search was performed using PubMed and MEDLINE databases to identify studies that discuss endometriomas and assisted reproductive technology before versus after surgery. RESULTS: In women with an endometrioma requiring ART, growing evidence suggests that surgery might result in damage to the ovarian reserve and further decrease chances of fertility. However, pregnancy rates, implantation rates, fertilization rates, and live birth rates seemed to be consistently similar across both groups. CONCLUSION: The current evidence is inconclusive on whether endometriomas should be surgically removed prior to ART. Further large randomized controlled trials are needed for a definite answer, and until then, management should be individualized.

Adenomyosis and infertility.

PURPOSE: Adenomyosis is a poorly understood entity with no unified treatment protocol. It has been thought to only affect the quality of life of older women, but growing evidence is highlighting the increased frequency of adenomyosis in younger patients and its possible effects on fertility outcomes. This can have a great impact on how clinicians screen, diagnose, and treat this condition. The aim of this review is to explore the relationship between adenomyosis and infertility. METHODS: A literature search of the keywords "adenomyosis", "infertility", "pregnancy" and "fertility" was conducted using the PubMed and Medline search engines. The articles selected were observational, systematic reviews, meta-analyses, and randomized controlled trials. The search was limited to English, abstracts were screened, and articles were selected. RESULTS: The literature reports lower clinical pregnancy rates, lower live birth rates, higher miscarriage rates, and higher odds of adverse obstetric outcomes in patients with adenomyosis. Treatment seems to be associated with higher pregnancy rates and live births rates. CONCLUSION: An association between adenomyosis and infertility seems to exist, and treatment could lead to improved fertility outcomes.

Validation of the French IVF guidelines during the COVID-19 pandemic.

RESEARCH QUESTION: Is a symptom questionnaire as per the French IVF guidelines adequate for screening patients during the COVID-19 pandemic? DESIGN: Patients planning IVF from June 2020 to February 2021 were included in the study. In compliance with French IVF guidelines, all patients fever-free on the day of oocyte retrieval were screened for risk of COVID-19 by completing a symptom questionnaire after being counselled regarding the importance of a COVID-19-free medical practice. Patients with IVF planned between June and September 2020 only completed the questionnaire (group 1), while those planning IVF after September 2020 also underwent the RT-PCR test for SARS-CoV-2 RNA (group 2). Cycle cancellation rates between groups were compared. Group 1 patients consented for follicular fluid testing for SARS-CoV-2 and an interview after cycle completion to determine COVID-19 exposure during the 6 months before and after retrieval. RESULTS: Cycle cancellation rates for groups 1 and 2 were 0% (0/214) versus 1.4% (8/577), respectively, (P = 0.116). All 183 follicular fluid samples from group 1 were negative for SARS-CoV-2 RNA. Of 171 patients interviewed post-IVF, 16 (93.4%) developed COVID-19 symptoms or a positive real-time PCR (RT-PCR) RT-PCR test, but none within 2 months pre- or post-retrieval. CONCLUSIONS: These results provide reassurance that, consistent with the COVID-19 French IVF guidelines, use of a symptom questionnaire is effective in screening patients planning to undergo IVF. Failure to detect viral RNA in any follicular fluid sample does not negate the possibility that follicular fluid is a viral reservoir. However, the findings provide reassurance that the follicular environment in this study's carefully screened population was COVID-free.

Recurrent implantation failure: how common is it?

PURPOSE OF REVIEW: To clarify a lingering issue, the true incidence of repeated implantation failures (RIF) in women undergoing successive frozen euploid single embryo transfers (FE-SET). RECENT FINDINGS: As not all Assisted reproductive techinique (ART) attempts are crowned by success, it has been questioned since incept of ART whether failures resulted from an embryonic or endometrial cause. RIF has received no precise definition but a trend has existed toward setting a more stringent definition, as reproductive biology has become more effective and ART success rates improved. No scientific society has yet convened on a universally accepted definition. The advent of effective and well tolerated pregestational testing of embryos for aneuploidy (PGT-A) has allowed to not transfer aneuploid embryos, which are bound not to succeed. This, therefore, justify revisiting the concept of RIF when only euploid embryos are transferred. SUMMARY: Contrary to lingering beliefs, the results of our study indicate that RIF following three successive euploid embryo transfers in a morphologically normal endometrium is a rare occurrence (<5%). This supports the concept that ART failures mainly result from embryonic causes. Our data also propose a new - functional - definition of RIF being an ART failure following 3 successive FE-SET attempts. Our findings, therefore seriously question the soundness of prescribing the often complex and expensive endometrial testing procedures that largely publicized for treating RIF.

Sacrospinous ligament fixation: medium and long-term anatomical results, functional and quality of life results.

BACKGROUND: To evaluate the medium and long-term anatomical results of sacrospinous ligament fixation (SLF) and its impact on quality of life (QoL). METHODS: We conducted a retrospective and observational single centre study. Fifty-nine patients were interviewed using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire and underwent physical examination using POP-Q several years after SLF. Primary outcome was the comparison of anatomic results of SLF at medium-term (group 1: 1-5 years after surgery) and long-term (group 2: more than 5 years after surgery). The secondary outcome was QoL evaluation. RESULTS: The overall recurrence and complication rates were respectively 22% and 10%, with no significant differences between groups 1 and 2. The recurrence rate was similar in both groups [twelve (35%) in group 1 and nine (20%) in group 2, p = 0.09]. Two patients (12%) in the recurrence and none in the no recurrence group had clinical symptoms (p = 0.08). Two patients (12%) in the recurrence and one patient (2%) in the no-recurrence group had a significant impact on their quality of life (p = 0.12). CONCLUSION: This study showed sustainable anatomic and functional results of SLF in medium and long-term analysis with overall low morbidity.

Is there a link between plasma progesterone 1-2 days before frozen embryo transfers (FET) and ART outcomes in frozen blastocyst transfers?

OBJECTIVE: To study the efficacy of combined administration of subcutaneous and vaginal progesterone for priming frozen blastocysts transfers, looking at progesterone levels and ART outcome. DESIGN: Retrospective study. SETTING PATIENTS: Three hundred and twenty frozen blastocyst transfer cycles conducted in 213 women aged up to 42 years, BMI between 18 and 30 kg/m2, with anatomically normal uterus who underwent frozen embryo transfers (FETs) from February 2019 to December 2019 with a combined luteal-phase support (LPS) associating subcutaneous and vaginal progesterone. Patients with recurrent pregnancy loss (RPL) were excluded. RESULTS: When using combined vaginal and subcutaneous LPS, SPL >10.50 ng/mL in 95% of cases, with a minimum value of 7.02 ng/mL. CPR, OPR, and global miscarriage rates were 38.4%, 30.9%, and 19.5%, respectively. Analyzing results per quartiles, revealed that miscarriage rates were significantly inferior, and IR were higher in the upper two quartiles of serum progesterone (>21.95 ng/mL) on the day before FET, while there was no difference in CPR and OPR. CONCLUSIONS: We report ART outcome of frozen blastocyst transfers performed using a combination of vaginal and subcutaneous progesterone for LPS. ART results were honorable and SPL favorable 1-2 days before FET in 99% of cases.

Utilization of in vitro maturation in cases with a FSH receptor mutation.

PURPOSE: To identify the FSH receptor (FSHR) variant and efficacy of in vitro maturation (IVM) in a 28-year-old woman with secondary amenorrhea, primary infertility, and ovarian resistance to FSH, and to analyze the genotype-to-phenotype relationship in cases of FSHR mutation for the development of an IVM algorithm for use in patients with gonadotropin resistance syndrome (GRS). METHODS: Oocytes retrieved after menstruation induction with norethisterone, followed by daily estrogen and an ovulatory trigger, underwent IVM, ICSI, and culture in a time-lapse (TL) incubator. Embryo transfers were performed on day 2, and after thawing on day 5. Genes associated with disorders of sex development were sequenced for both the patient and her parents. All reported cases of FSHR mutation were analyzed to investigate genotype/phenotypic relationships. RESULTS: After ovum pickup, seven of 16 oocytes matured and all fertilized. After unsuccessful day 2 transfer, our patient delivered with a thawed day 5 blastocyst, the sole embryo without abnormal TL phenotypes. Genetic analysis revealed a new composite heterozygous FSHR variant. Analysis of our patient case with published cases of GRS revealed associations among FSHR variant genotype, location on the FSHR, functionality of tested variants, and type of amenorrhea. An algorithm for application of IVM for GRS patients was developed. CONCLUSIONS: We report two novel variants of the FSHR. Although IVM successfully matured some oocytes, only one resulted in an embryo with normal TL phenotypes. We recommend FSHR genetic testing in GRS patients, which will help guide their suitability for IVM.

Uterus transplantation worldwide: clinical activities and outcomes.

PURPOSE OF REVIEW: Women with absolute uterine factor infertility, because of uterine absence, or the presence of a nonfunctional uterus, were regarded as being untreatable until 2014 when the first birth following uterus transplantation (UTx) took place in Sweden. This proof-of-concept occurred in a woman with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHs) with congenital uterine absence, who received a uterus from a 61-year-old live donor (LD). Since then, several births after UTx have occurred in Sweden and subsequently in other countries, including both LD and deceased donor (DD) transplants. A great majority of the recipients were women with MRKHs. The efficiency and safety of UTx can be determined only when a complete study cohort of transplanted women have reached the definitive endpoint of graft hysterectomy. The different outcomes of transplanted women include graft failure, as well as graft survival with failure to achieve livebirth, or livebirth(s). Published data from a completed trial are not yet available. The results that we have to rely on are reports of completed surgeries and interim outcomes that may be as early as a few months after surgery and up to several years after UTx. The purpose of this review is to give an update on all published clinical UTx data and major results, including live births up to mid 2021. RECENT FINDINGS: The interim results of a number of UTx studies have been published. LD UTx procedures have been reported from four European countries (Sweden, the Czech Republic, Germany, Spain), four Asian nations (Saudi Arabia, India, China, Lebanon), as well as some from the USA. DD UTx procedures have been reported from Turkey, the Czech Republic, the USA and Brazil. To our knowledge, there also exist unpublished UTx cases from some of the countries mentioned above and from at least four other countries (Serbia, France, Mexico, Italy). We estimate that at least 80 UTx procedures have been performed, resulting in more than 40 births. The present study includes only data from published, peer-reviewed, research papers. The results of 62 UTx cases show an overall surgical success rate, as defined by a technically successful transplantation with a subsequent regular menstrual pattern, of 76%. The success rates for LD and DD UTx procedures were 78% and 64%, respectively. The rate of serious postsurgical complications requiring invasive or radiological intervention was 18% for LDs and 19% for recipients. The cumulative live birth rate in successful UTx procedures is estimated to be above 80%. Twenty-four births after UTx have been reported and the results show a high rate of preterm birth, with an associated high proportion of respiratory distress syndrome. SUMMARY: UTx has proven to be a successful treatment for uterine factor infertility at several centers around the world. The modest success rate and the fairly high complication rate among LDs, indicate that further research and development under strict governance are needed before this option should be widely offered.

A high level of tetrasomy 9p mosaicism but no clinical manifestations other than moderate oligozoospermia with chromosomally balanced sperm: a case report.

Tetrasomy 9p (ORPHA: 3310) (i(9p)) is a rare chromosomal imbalance. It is characterized by the presence of a supernumerary chromosome incorporating two copies of the short arm of chromosome 9 and is usually present in a mosaic state postnatally. Depending on the level of mosaicism, the phenotype ranges from mild developmental delay to multiple congenital anomalies with severe intellectual disability. Here, we report on a patient diagnosed with i(9p) mosaicism after the recurrent failure of in vitro fertilization. Although the patient's clinical phenotype was normal, the level of mosaicism varied greatly from one tissue to another. A sperm analysis evidenced subnormal spermatogenesis with chromosomally balanced spermatozoa and no risk of transmission to the offspring. Although individuals with i(9p) and no clinical manifestations have rarely been described, the prenatal diagnosis of this abnormality in the absence of ultrasound findings raises a number of questions.

Managing an obstetrics and gynaecology department in time of COVID pandemic: safety and efficacy first at Foch hospital.

Obstetrics and Gynecology department in France were not ready for the outbreak of the COVID pandemic, but ingenuity and dedication of personnel allowed to perform safely and avoid nocomial transmission of COVID.

Simulation and professional development: added value of 3D modelization in reproductive endocrinology and infertility and assisted reproductive technologies teamwork.

As in other specialties of medicine, there is more to clinical performance in reproductive endocrinology, infertility, and assisted reproductive technologies (REI-ART) than simply the individual knowledge and technical skills. Simulation is commonly used during fellowship training in REI-ART, aiming to produce a virtual cycle of professional development in order to improve patient outcome. With scientific certification and the joint development of evaluation tools, the contribution of digitalization, such as 3 D printing and digital simulators, will facilitate teamwork in REI-ART and enable a better transmission of knowledge in the specialty.