Medically Assisted Reproduction Research Articles

Companies should care about the health troubles of their employees. The results of a French survey on medically assisted reproduction (MAR)

Several factors can deeply affect employees’ quality of life at work. Work-life balance, subjective well-being and job satisfaction are three of these factors and it is in the best interest of companies to handle these topics carefully. This is a sine qua non condition of the strength and the quality of relationships with employees. It is also a source of confidence for employees, especially where this is being mediated through Human Resource (HR) processes. Our article studies the quality of life at work in the particular context of an MAR healthcare pathway that exacerbates the consequences for employees. Our work with hundreds of people enduring an MAR process shows that depending on whether firms take this situation into account or not, employees will feel either well-being or ill-being and will have different burnout or job satisfaction levels. All these variables influence their commitment and job performance. These links between a healthcare pathway and quality of life at work on the one hand, and between the quality of work and performance on the other hand, should lead employers to support employees in a personal vulnerable situation. The strength and the quality of the support provided by the HR function and the management is therefore a key point in the level of confidence that exists between firms and their employees.

Medically Assisted Reproduction and Risk of Cancer Among Offspring

Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations. To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally. For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023. Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI). The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth. This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years). The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.

The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.

Differences in medically assisted reproduction use by sexual identity and partnership: a prospective cohort of cisgender women.

Does medically assisted reproduction (MAR) use among cisgender women differ among those with same-sex partners or lesbian/bisexual identities compared to peers with different-sex partners or heterosexual identities? Women with same-sex partners or lesbian/bisexual identities are more likely to utilize any MAR but are no more likely to use ART (i.e. IVF, reciprocal IVF, embryo transfer, unspecified ART, ICSI, and gamete or zygote intrafallopian transfer) compared to non-ART MAR (i.e. IUI, ovulation induction, and intravaginal or intracervical insemination) than their different-sex partnered and completely heterosexual peers. Sexual minority women (SMW) form families in myriad ways, including through fostering, adoption, genetic, and/or biological routes. Emerging evidence suggests this population increasingly wants to form genetic and/or biological families, yet little is known about their family formation processes and conception needs. The Growing Up Today Study is a US-based prospective cohort (n = 27805). Participants were 9-17 years of age at enrollment (1996 and 2004). Biennial follow-up is ongoing, with data collected through 2021. Cisgender women who met the following criteria were included in this sample: endorsed ever being pregnant; attempted a pregnancy in 2019 or 2021; and endorsed either a male- or female-sex partner OR responded to questions regarding their sexual identity during their conception window. The main outcome was any MAR use including ART (i.e. procedures involving micromanipulation of gametes) and non-ART MAR (i.e. nonmanipulation of gametes). Secondary outcomes included specific MAR procedures, time to conception, and trends across time. We assessed differences in any MAR use using weighted modified Poisson generalized estimating equations. Among 3519 participants, there were 6935 pregnancies/pregnancy attempts and 19.4% involved MAR. A total of 47 pregnancies or pregnancy attempts were among the same-sex partnered participants, while 91 were among bisexual participants and 37 among lesbian participants. Participants with same-sex, compared to different-sex partners were almost five times as likely to use MAR (risk ratio [95% CI]: 4.78 [4.06, 5.61]). Compared to completely heterosexual participants, there was greater MAR use among lesbian (4.00 [3.10, 5.16]) and bisexual (2.22 [1.60, 3.07]) participants compared to no MAR use; mostly heterosexual participants were also more likely to use ART (1.42 [1.11, 1.82]) compared to non-ART MAR. Among first pregnancies conceived using MAR, conception pathways differed by partnership and sexual identity groups; differences were largest for IUI, intravaginal insemination, and timed intercourse with ovulation induction. From 2002 to 2021, MAR use increased proportionally to total pregnancies/pregnancy attempts; ART use was increasingly common in later years among same-sex partnered and lesbian participants. Our results are limited by the small number of SMW, the homogenous sample of mostly White, educated participants, the potential misclassification of MAR use when creating conception pathways unique to SMW, and the questionnaire's skip logic, which excluded certain participants from receiving MAR questions. Previous studies on SMW family formation have primarily focused on clinical outcomes from ART procedures and perinatal outcomes by conception method, and have been almost exclusively limited to European, clinical samples that relied on partnership data only. Despite the small sample of SMW within a nonrepresentative study, this is the first study to our knowledge to use a nonclinical sample of cisgender women from across the USA to elucidate family formation pathways by partnership as well as sexual identity, including pathways that may be unique to SMW. This was made possible by our innovative approach to MAR categorization within a large, prospective dataset that collected detailed sexual orientation data. Specifically, lesbian, bisexual, and same-sex partnered participants used both ART and non-ART MAR at similar frequencies compared to heterosexual and different-sex partnered participants. This may signal differential access to conception pathways owing to structural barriers, emerging conception trends as family formation among SMW has increased, and a need for conception support beyond specialized providers and fertility clinics. The research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH), under award number R01MD015256. Additionally, KRSS is supported by NCI grant T32CA009001, AKH by the NCI T32CA057711, PC by the NHLBI T32HL098048, BM by the Stanford Maternal Child Health Research Institute Clinical Trainee Support Grant and the Diversity Fellowship from the American Society for Reproductive Medicine Research Institute, BGE by NICHD R01HD091405, and SM by the Thomas O. Pyle Fellowship through the Harvard Pilgrim Health Care Foundation and Harvard University, NHLBI T32HL098048, NIMH R01MH112384, and the William T. Grant Foundation grant number 187958. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The first author recently had a leadership role in the not-for-profit program, The Lesbian Health Fund, a research fund focused on improving the health and wellbeing of LGBTQ+ women and girls. The fund did not have any role in this study and the author's relationship with the fund did not bias the findings of this manuscript. N/A.

Consumption of hookahs, e-cigarettes, and classic cigarettes and the impact on medically assisted reproduction treatment

Smoking of classic cigarettes has been well-established as a health risk factor, including cardiovascular, neurological, and pulmonary diseases. Adverse effects on human reproduction have also been shown. Smokers are assumed to have a significantly lower chance of pregnancy, however, the impact of smoking on medically assisted reproduction (MAR) treatment outcomes is controversial. Moreover, smoking habits have changed during the last decades since e-cigarettes and hookahs, or water pipes, have become very popular, yet little is known regarding vaping or hookah-smoking patients undergoing MAR treatments. This prospective study aimed to examine the presence of benzo[a]pyrene, nicotine, and its main metabolite, cotinine, in human follicular fluid (FF) in non-smoking, smoking, and vaping/hookah-smoking patients and to evaluate the impact on female fertility. Human FF samples were collected from 320 women subjected to intracytoplasmic sperm injection (ICSI) cycles due to male subfertility. Gas chromatography combined with mass spectrometry was used to analyse the presence of benzo[a]pyrene, nicotine, and cotinine. A questionnaire was provided to assess patient consumption behaviour and to identify (1) non-smoking patients, (2) patients who consumed cigarettes, and (3) patients with exclusive consumption of e-cigarettes or hookahs. Data were analysed using linear and logistic regression, Fisher’s exact test, and the Mann–Whitney U Test. Nicotine was present in 22 (6.8%) and cotinine in 65 (20.3%) of the 320 samples. The nicotine and cotinine concentrations per sample ranged from 0 to 26.3 ng/ml and 0–363.0 ng/ml, respectively. Benzo[a]pyrene was not detectable in any of the samples analysed. Nicotine and cotinine were also present in the FF of patients with exclusive consumption of e-cigarettes or hookahs. The clinical pregnancy rate, fertilization and maturation rates, and number of oocytes per oocyte pick-up were not statistically significantly different between non-smoking, smoking, or vaping/hookah-smoking patients. Smoking and the accumulation of smoking toxins in the FF have no impact on the outcome of MAR treatments—neither the clinical pregnancy rate, maturation and fertilization rates, nor the number of retrieved oocytes were affected. For the first time, nicotine and cotinine were quantified in the FF of patients exclusively vaping e-cigarettes or smoking hookahs. Since vaping liquids and hookah tobaccos contain potentially harmful substances, other adverse effects cannot be excluded.Trial registration ClinicalTrials.gov Identifier: NCT03414567.

Single mothers by choice - experiences of single women seeking treatment at a public fertility clinic in Denmark: A pilot study

ProblemThere has been an increase in the number of single women deciding to have children through the use of medically assisted reproduction (MAR). These women are referred to as ‘single mothers by choice’ (SMC). Background: Previous studies have shown how SMC can feel stigmatised. Aim: Explore if single women seeking fertility treatment in Denmark feel stigmatised. MethodsSix single women undergoing MAR at a public fertility clinic in Denmark were interviewed. The interviews were audiotaped, anonymised, and transcribed in full, after provided written consent by the participants to take part in the study. Data were analysed using qualitative content analysis. FindingsThe women would have preferred to have a child in a relationship with a partner. Despite their dream of the nuclear family meaning a family group consisting of two parents and their children (one or more), the women choose to become SMC because motherhood was of such importance, and they feared they would otherwise become too old to have children. The participants did not experience stigma or negative responses to their decision, but they all had an awareness of the prejudices other people might have towards SMC. ConclusionThis study contributes to the understanding of the experiences of single women seeking fertility treatment in a welfare state where there are no differences in the possibilities for different social classes to seek MAR.

Preparing solo mothers for childbirth and parenthood – The importance of being with like-minded women

ObjectivesDenmark and many high-income countries have seen an increase in the number of single women getting pregnant through medical assisted reproduction (MAR). These women are also named solo mothers. According to the Danish Health Authorities, they should, as all other pregnant women, be offered antenatal education. The aim of this study was to explore solo mothers’ needs in order to prepare them for childbirth and parenthood. MethodsThis qualitative study was set to investigate solo mothers’ experiences and requirements during pregnancy toprepare them for childbirth and parenting. Semi-structured interviews were conducted by telephone or face-to-face. A systematic text condensation and interpretation was used to analyse data. Results38 interviews were conducted before and after pregnancy. Twenty solo mothers participated in the study. Three themes emerged from the analysis: ‘Confrontation with the normative pregnancy’, ‘Mirroring and network’ and ‘Using formal and informal sources to gain information’. ConclusionThe conventional antenatal packages offered by the healthcare system did not meet the solo mothers’ needs. The women called for content and information tailored to single parents. Solo mothers may benefit from structured antenatal classes in small groups. Being with like-minded women was essential for preparing for childbirth and parenting.

Health needs, treatment decisions and experience of traditional complementary and integrative medicine use by women with diminished ovarian reserve: Across-sectional survey.

Women with diminished ovarian reserve (DOR) have fewer eggs than would be expected at their age. It is estimated that 10% of women seeking fertility treatment are diagnosed with DOR. However, the success rate of medically assisted reproduction (MAR) is significantly lower in women with DOR, thus many seek additional approaches. To explore the health needs of women with DOR, treatment options and experience of treatment including traditional complementary integrative medicine (TCIM). Anyone with a diagnosis of DOR, living in Australia or New Zealand, aged over 18 were invited to complete an online survey distributed via fertility support networks and social media platforms from April to December 2021. Data from 67 respondents were included. The main aspects of health that were impacted by DOR were fertility (91.0%) and mental health (52.2%). The main treatment recommended was MAR with most women either currently using MAR (38.8%) or having previously used MAR (37.3%). TCIM was widely used with 88.1% of women utilising supplements, 74.6% consulting with TCIM practitioners, and 65.7% adopting self-care practices. The main reasons for using TCIM were to improve fertility or support pregnancy, and to support general health and well-being. Women with DOR have additional health needs apart from infertility, most notably mental health support. The main form of treatment utilised is MAR, despite DOR being challenging for fertility clinicians. TCIM was widely used, and respondents perceived benefits related to improving fertility, supporting pregnancy, or improving well-being through use of acupuncture, meditation, naturopathy, massage, yoga.

Estimating the impact of bias in causal epidemiological studies: the case of health outcomes following assisted reproduction.

Researchers interested in causal questions must deal with two sources of error: random error (random deviation from the true mean value of a distribution), and bias (systematic deviance from the true mean value due to extraneous factors). For some causal questions, randomization is not feasible, and observational studies are necessary. Bias poses a substantial threat to the validity of observational research and can have important consequences for health policy developed from the findings. The current piece describes bias and its sources, outlines proposed methods to estimate its impacts in an observational study, and demonstrates how these methods may be used to inform debate on the causal relationship between medically assisted reproduction (MAR) and health outcomes, using cancer as an example. In doing so, we aim to enlighten researchers who work with observational data, especially regarding the health effects of MAR and infertility, on the pitfalls of bias, and how to address them. We hope that, in combination with the provided example, we can convince readers that estimating the impact of bias in causal epidemiologic research is not only important but necessary to inform the development of robust health policy and clinical practice recommendations.

Building families through MAR (medically assisted reproduction), donor conception and surrogacy: Where does this fit into clinical psychology?

In the following account, the author reflects on her experiences with individuals and families who have used Medically Assisted Reproduction (MAR) in order to create their families. The article covers some of the history of this constantly developing field, the legislation and regulations in the UK, and some of the inherent complexities. She suggests that Clinical Psychologists need to know more about this area, in order to respond appropriately to those they assess and treat, as in all specialties, issues relating to conception may have a relevance to the issues to be addressed.

Identification of two hidden clinical subgroups among men with idiopathic cryptozoospermia.

Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies? We reveal two distinct subgroups of cryptozoospermic (Crypto) patients based on testicular tissue composition, testicular volume, and FSH levels. Cryptozoospermic patients present with a sperm concentration below 0.1 million/ml. While the etiology of the severely impaired spermatogenesis remains largely unknown, alterations of the spermatogonial compartment have been reported including a reduction of the reserve stem cells in these patients. To assess whether there are distinct subgroups among cryptozoospermic patients, we applied the statistical method of cluster analysis. For this, we retrospectively selected 132 cryptozoospermic patients from a clinical database who underwent a testicular biopsy in the frame of fertility treatment at a university hospital. As controls (Control), we selected 160 patients with obstructive azoospermia and full spermatogenesis. All 292 patients underwent routine evaluation for endocrine, semen, and histological parameters (i.e. the percentage of tubules with elongated spermatids). Moreover, outcome of medically assisted reproduction (MAR) was assessed for cryptozoospermic (n = 73) and Control patients (n = 87), respectively. For in-depth immunohistochemical and histomorphometrical analyses, representative tissue samples from cryptozoospermic (n = 27) and Control patients (n = 12) were selected based on cluster analysis results and histological parameters. This study included two parts: firstly using clinical parameters of the entire cohort of 292 patients, we performed principal component analysis (PCA) followed by hierarchical clustering on principal components (i.e. considering hormonal values, ejaculate parameters, and histological information). Secondly, for histological analyses seminiferous tubules were categorized according to the most advanced germ cell type present in sections stained with Periodic acid Schif. On the selected cohort of 39 patients (12 Control, 27 cryptozoospermic), we performed immunohistochemistry for spermatogonial markers melanoma-associated antigen 4 (MAGEA4) and piwi like RNA-mediated gene silencing 4 (PIWIL4) followed by quantitative analyses. Moreover, the morphologically defined Adark spermatogonia, which are considered to be the reserve stem cells, were quantified. The PCA and hierarchical clustering revealed three different clusters, one of them containing all Control samples. The main factors driving the sorting of patients to the clusters were the percentage of tubules with elongated spermatids (Cluster 1, all Control patients and two cryptozoospermic patients), the percentage of tubules with spermatocytes (Cluster 2, cryptozoospermic patients), and tubules showing a Sertoli cells only phenotype (Cluster 3, cryptozoospermic patients). Importantly, the percentage of tubules containing elongated spermatids was comparable between Clusters 2 and 3. Additional differences were higher FSH levels (P < 0.001) and lower testicular volumes (P < 0.001) in Cluster 3 compared to Cluster 2. In the spermatogonial compartment of both cryptozoospermic Clusters, we found lower numbers of MAGEA4+ and Adark spermatogonia but higher proportions of PIWIL4+ spermatogonia, which were significantly correlated with a lower percentage of tubules containing elongated spermatids. In line with this common alteration, the outcome of MAR was comparable between Controls as well as both cryptozoospermic Clusters. While we have uncovered the existence of subgroups within the cohort of cryptozoospermic patients, comprehensive genetic analyses remain to be performed to unravel potentially distinct etiologies. The novel insight that cryptozoospermic patients can be divided into two subgroups will facilitate the strategic search for underlying genetic etiologies. Moreover, the shared alterations of the spermatogonial stem cell compartment between the two cryptozoospermic subgroups could represent a general response mechanism to the reduced output of sperm, which may be associated with a progressive phenotype. This study therefore offers novel approaches towards the understanding of the etiology underlying the reduced sperm formation in cryptozoospermic patients. German research foundation CRU 326 (grants to: SDP, NN). Moreover, we thank the Faculty of Medicine of the University of Münster for the financial support of Lena Charlotte Schülke through the MedK-program. We acknowledge support from the Open Access Publication Fund of the University of Münster. The authors have no potential conflicts of interest. N/A.

Medically assisted reproduction in Italy, 2020 data from the Italian MAR Register.

The Italian Medically Assisted Reproduction (MAR) Register (ItMARR) was established by the Decree of the Minister of Health issued on October 7th, 2005. ItMARR has a crucial role in clearly and publicly disseminating epidemiological information on the MAR activities and outcomes. ItMARR data is collected in aggregate form and is mandatory as set out in Law 40/2004. The aim of this article is to make a snapshot of the authorized centers that perform IUI and ART in Italy. Data used in this article refer to MAR treatments started between January 1st and December 31st, 2020. MAR techniques were performed by 332 centers. In total, 67,927 ART cycles and 12,171 IUI cycles were performed in 2020. Gametes donation cycles represent 12.9% of ART activity and 4.0% of IUI. ART cycles performed per million women of childbearing age was 6525. In 2020, 2.5% of births in the general population in Italy were a result of application of ART techniques. MAR activity in 2020, has been heavily reduced by the limitations to reproductive treatment due to SARS-CoV-2 pandemic. Pregnancy rates per transfers were 26.7% with fresh techniques, 32.6% with FER, 25.7% with FO, 38.0% with OD and 39.1% with SD. There were fewer multiple deliveries than the previous year. The ItMARR, has become a great asset in the reproductive health scenario promoting a better MAR information dissemination. ItMARR is working on the implementation towards a "cycle-by-cycle" data collection system. This will bring the Italian monitoring system in line with others European countries.

The risk of perinatal and cardiometabolic complications in pregnancies conceived by medically assisted reproduction

PurposeTo examine the impact of medically assisted fertility treatments on the risk of developing perinatal and cardiometabolic complications during pregnancy and in-hospital deliveries.MethodsWe conducted a retrospective cohort study using medical health records of deliveries occurring in 2016–2022 at a women’s specialty hospital in a southern state of the Unites States (US). Pregnancies achieved using medically assisted reproductive (MAR) techniques were compared with unassisted pregnancies using propensity score matching (PSM), based on demographic, preexisting health, and reproductive factors. Study outcomes included cesarean delivery, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), delivery complications, and postpartum readmission. We used Poisson regression with robust standard errors to generate risk ratios (RRs) and 95% confidence intervals (CIs) for all study outcomes.ResultsAmong 57,354 deliveries, 586 (1.02%) pregnancies were achieved using MAR and 56,768 (98.98%) were unassisted (“non-MAR”). Compared to the non-MAR group, MAR pregnancies had significantly higher prevalence of all study outcomes, including GDM (15.9% vs. 11.2%, p < 0.001), HDP (28.2% vs. 21.1%, p < 0.001), cesarean delivery (56.1% vs. 34.6%, p < 0.001), delivery complications (10.9% vs. 6.8%, p = 0.03), and postpartum readmission (4.3% vs. 2.7%, p = 0.02). In a PSM sample of 584 MAR and 1,727 unassisted pregnancies, MAR was associated with an increased risk of cesarean delivery (RR = 1.11, 95% CI = 1.01–1.22); whereas IVF was associated with an increased risk of cesarean delivery (RR = 1.15, 95% CI = 1.03–1.28) and delivery complications (RR = 1.44, 95% CI = 1.04–2.01).ConclusionsWomen who conceived with MAR were at increased risk of cesarean deliveries, and those who conceived with IVF were additionally at risk of delivery complications.

Impacts of COVID-19 on Medically Assisted Live Birth Rates in the United States in 2020 and 2021

Initial declines in births due to medically assisted reproduction (MAR) in December 2020 have been documented. However, the longer-term impact of COVID-19 on U.S. MAR birth rates has not yet been evaluated. Negative-binomial regression analyses were employed using counts of MAR births from the National Vital Statistics System and female population counts from the Current Population Survey as the exposure variable. Interaction terms were used to investigate whether trends varied by sociodemographic groups. The descriptive analyses showed sharp declines in the percentage of births due to MAR in December 2020 (1.05%) and January 2021 (1.08%). Multivariable negative-binomial regression showed the incident rates of MAR births were lower in December 2020 relative to all other periods with the exception of January 2021 (IRR = 0.97, 95% Confidence Interval: 0.77–1.22). Negative-binomial regression analyses with interaction terms found the decline and rebound in MAR births differed by educational attainment. Overall, however, the yearly incidence rates of MAR births in 2020 and 2021 were not different from rates from prior years (2017–2019). Thus, COVID-19 service suspension likely had a substantive effect on U.S. MAR birth rates, but this reduction quickly rebounded to pre-pandemic levels. This study extends prior research, which focused on data from 2020, and sheds further light on behavior related to MAR use and its potential demographic implications during the pandemic.

Exploring attitudes and experiences with reproductive genetic carrier screening among couples seeking medically assisted reproduction: a longitudinal survey study.

This study aimed to assess the attitudes and experiences of subfertile couples applying for medically assisted reproduction (MAR) using their own gametes towards reproductive genetic carrier screening (RGCS) for monogenic conditions. A prospective survey study was conducted where subfertile couples were recruited from the fertility centre of a university hospital in Flanders, Belgium. Participants were offered RGCS free of charge and completed self-administered questionnaires at three different time points. The study sample consisted of 26 couples. Most participants had no children, did not consider themselves as religious, and had some form of higher education. Overall, attitudes towards RGCS were mostly positive and the intention to participate in RGCS was high. Anxiety scores were only elevated and clinically relevant for a limited number of participants. A large proportion of participants would consider preventive reproductive options like prenatal diagnosis or in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) combined with pre-implantation genetic testing for monogenic conditions (PGT-M) in the event of an increased likelihood of conceiving a child with a hereditary condition. Participants were satisfied with their decision to undergo RGCS, and the majority would recommend RGCS to other couples. Our study findings suggest that subfertile couples applying for MAR using their own gametes find RGCS acceptable and have a positive attitude towards it. This study provides valuable insights into the perspectives of these couples, highlighting the need for appropriate counseling and timely information provision.

Maternal education and its association with maternal and neonatal adverse outcomes in live births conceived using medically assisted reproduction (MAR)

BackgroundTo examine the association between maternal education and adverse maternal and neonatal outcomes in women who conceived using medically assisted reproduction, which included fertility medications, intrauterine insemination, or in vitro fertilization.MethodsWe conducted a retrospective cohort study utilizing the US Vital Statistics data set on national birth certificates from 2016 to 2020. Women with live, non-anomalous singletons who conceived using MAR and had education status of the birthing female partner recorded were included. Patients were stratified into two groups: bachelor’s degree or higher, or less than a bachelor’s degree. The primary outcome was a composite of maternal adverse outcomes: intensive care unit (ICU) admission, uterine rupture, unplanned hysterectomy, or blood transfusion. The secondary outcome was a composite of neonatal adverse outcomes: neonatal ICU admission, ventilator support, or seizure. Multivariable modified Poisson regression models with robust error variance adjusted for maternal age, race, marital status, prenatal care, smoking during pregnancy, neonatal sex, and birth year estimated the relative risk (RR) of outcomes with a 95% confidence interval (CI).Results190,444 patients met the inclusion criteria: 142,943 had a bachelor’s degree or higher and 47,501 were without a bachelor’s degree. Composite maternal adverse outcomes were similar among patients with a bachelor’s degree (10.1 per 1,000 live births) and those without a bachelor’s degree (9.4 per 1,000 live births); ARR 1.05, 95% CI (0.94–1.17). However, composite adverse neonatal outcomes were significantly lower in women with a bachelor’s degree or higher (94.1 per 1,000 live births) compared to women without a bachelor’s degree (105.9 per 1,000 live births); ARR 0.91, 95% CI (0.88–0.94).ConclusionsOur study demonstrated that lower maternal education level was not associated with maternal adverse outcomes in patients who conceived using MAR but was associated with increased rates of neonatal adverse outcomes. As access to infertility care increases, patients who conceive with MAR may be counseled that education level is not associated with maternal morbidity. Further research into the association between maternal education level and neonatal morbidity is indicated.

[The revision of the Bioethics Act, two years on: major principles and consequences for practice in the reproductive biology laboratory].

Since 1994, in France, bioethics law has set the regulatory framework for Medically Assisted Reproduction (MAR). The latest revision of the law of August 2, 2021, is characterized by major upheavals in the field of MAR and intervenes in several areas: the purpose and conditions to access to MAR, access to origins in the case of gamete or embryo donation, and gametes cryopreservation without medical indication. Indeed, the law authorizes, because of a strong societal demand, the extension of sperm donation to couples of women and unmarried women, as well as the possibility for any person to preserve his/her gametes if he/she meets the age criteria defined by decree. Finally, the law opens the possibility for people born following gamete or embryo donation to have access, from their 18th anniversary, to identifying and/or non-identifying data. These new measures have led to a very important number of MAR requests to fertility and donation centers, and have required the implementation of new circuits in order to harmonize care, without discrimination or prioritization.

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 (KP54) can induce oocyte maturation during in vitro fertilization treatment, including in women at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. ObjectiveTo determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (Phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (Phase-2a trial). DesignTwo randomized, placebo-controlled, parallel group, dose-finding trials. SettingClinical trials unit, Netherlands. ParticipantsHealthy women aged 18-35 years, either without (Phase-1; n=24), or with ovarian stimulation (Phase-2a; n=75). InterventionsPhase-1: Single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n=6 per dose).Phase-2a: Single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n=16-17 per dose), triptorelin 0.2 mg (n=5; active comparator), or placebo (n=5). Main Objectives and Outcome MeasuresPhase-1: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones).Phase-2a: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); time to ovulation assessed by transvaginal ultrasound. ResultsIn both trials, MVT-602 was safe and well-tolerated across the entire dose-range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours.In the Phase-2a trial, LH concentrations increased dose-dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3μg MVT-602 and remained above 15 IU/L for 33 hours. Time to ovulation following drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1μg), 82% (0.3μg), and 75% (0.1μg), of women after MVT-602, 100% after triptorelin, and 60% after placebo. ConclusionsMVT-602 induces LH concentrations of similar amplitude and duration as the physiological mid-cycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR. Trial RegistrationsEUDRA-CT: 2017-003812-38, 2018-001379-20

Moonshots and last miles: what it may take to treat infertility for all

Innovation in medically assisted reproduction (MAR) is at an all-time high, with new technologies being developed for the laboratory and around the patient experience, and deployed quickly and effectively. Nevertheless, substantial improvements in the success of infertility care seem to elude the field. This article presents the view that MAR is missing the key innovation motor of mechanistic knowledge, which historically relates to a lack of public resources of the kind afforded to other diseases. It is posited that unless and until we raise infertility at the level of an urgent unmet medical need in the eyes of government and national funding body, innovation will be limited in scope and impact, and be incremental in nature.

ART in Europe, 2019: results generated from European registries by ESHRE†.

What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2019 as compared to previous years? The 23rd ESHRE report highlights the rising ART treatment cycles and children born, alongside a decline in twin deliveries owing to decreasing multiple embryo transfers; fresh IVF or ICSI cycles exhibited higher delivery rates, whereas frozen embryo transfers (FET) showed higher pregnancy rates (PRs), and reported IUI cycles decreased while maintaining stable outcomes. ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF-Monitoring (EIM) Consortium since 1997 and reported in a total of 22 manuscripts published in Human Reproduction and Human Reproduction Open. Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between 1 January and 31 December 2019 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in one of the 44 countries that are members of the EIM Consortium. Overall, 1487 clinics offering ART services in 40 countries reported, for the second time, a total of more than 1 million (1077813) treatment cycles, including 160782 with IVF, 427980 with ICSI, 335744 with FET, 64089 with preimplantation genetic testing (PGT), 82373 with egg donation (ED), 546 with IVM of oocytes, and 6299 cycles with frozen oocyte replacement (FOR). A total of 1169 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 147711) or donor semen (IUI-D; n = 51651) in 33 and 24 countries, respectively. Eighteen countries reported 24139 interventions in pre- and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. In 21 countries (21 in 2018) in which all ART clinics reported to the registry 476760 treatment cycles were registered for a total population of approximately 300 million inhabitants, allowing the best estimate of a mean of 1581 cycles performed per million inhabitants (range: 437-3621). Among the reporting countries, for IVF the clinical PRs per aspiration slightly decreased while they remained similar per transfer compared to 2018 (21.8% and 34.6% versus 25.5% and 34.1%, respectively). In ICSI, the corresponding PRs showed similar trends compared to 2018 (20.2% and 33.5%, versus 22.5% and 32.1%) When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.5% (28.8% in 2018) and 26.2% (27.3% in 2018) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was at 35.1% (versus 33.4% in 2018), and with embryos originating from donated eggs at 43.0% (41.8% in 2018). After ED, the PR per fresh embryo transfer was 50.5% (49.6% in 2018) and per FOR 44.8% (44.9% in 2018). In IVF and ICSI together, the trend toward the transfer of fewer embryos continues with the transfer of 1, 2, 3, and ≥4 embryos in 55.4%, 39.9%, 2.6%, and 0.2% of all treatments, respectively (corresponding to 50.7%, 45.1%, 3.9%, and 0.3% in 2018). This resulted in a reduced proportion of twin delivery rates (DRs) of 11.9% (12.4% in 2018) and a similar triplet DR of 0.3%. Treatments with FET in 2019 resulted in twin and triplet DR of 8.9% and 0.1%, respectively (versus 9.4% and 0.1% in 2018). After IUI, the DRs remained similar at 8.7% after IUI-H (8.8% in 2018) and at 12.1% after IUI-D (12.6% in 2018). Twin and triplet DRs after IUI-H were 8.7% and 0.4% (in 2018: 8.4% and 0.3%) and 6.2% and 0.2% after IUI-D (in 2018: 6.4% and 0.2%), respectively. Eighteen countries (16 in 2018) provided data on FP in a total number of 24139 interventions (20994 in 2018). Cryopreservation of ejaculated sperm (n = 11592 versus n = 10503 in 2018) and cryopreservation of oocytes (n = 10784 versus n = 9123 in 2018) were most frequently reported. Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. The 23rd ESHRE data collection on ART, IUI, and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts toward optimization of both the collection and the reporting, from the perspective of improving surveillance and vigilance in the field of reproductive medicine, are awaited. The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.