Internal validation of gestational age estimation algorithms in health-care databases using pregnancies conceived through fertility procedures.

Fertility procedures recorded in health-care databases can be used to estimate the start of pregnancy, which can serve as a reference standard to validate gestational age estimates based on International Classification of Diseases codes. In a cohort of 17 398 US MarketScan pregnancies (2011-2020) in which conception was achieved via fertility procedures, we estimated gestational age at the end of pregnancy using algorithms based on (1) time (days) since the fertility procedure (the reference standard); (2) International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) (before/after October 2015) codes indicating gestational length recorded at the end of pregnancy (method A); and (3) ICD-10 end-of-pregnancy codes enhanced with Z3A codes denoting specific gestation weeks recorded at prenatal visits (method B). We calculated the proportion of pregnancies with an estimated gestational age falling within 14 days ($\pm$14 days) of the reference standard. Method A accuracy was similar for ICD-9 and ICD-10 codes. After 2015, method B was more accurate than method A: For term births, within-14-day agreement was 90.8% for method A and 98.7% for method B. Corresponding estimates were 70.1% and 95.6% for preterm births; 35.3% and 92.6% for stillbirths; 54.3% and 64.2% for spontaneous abortions; and 16.7% and 84.6% for elective terminations. ICD-10-based algorithms that incorporate Z3A codes improve the accuracy of gestational age estimation in health-care databases, especially for preterm births and non-live births.

The role of multiple birth and birth complications in the association between assisted reproductive technology conception and autism diagnosis.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

Assisted Reproductive Technology, Multiple Births, and Perinatal Outcomes in Taiwan from 2001 to 2020.

OBJECTIVE: To investigate the effect of the Assisted Reproduction Act, implemented in 2007 in Taiwan to reduce the number of embryos to transfer, on the trends over time regarding the rate of multiple births, preterm delivery, low birth weight (LBW), and small for gestational age (SGA) among deliveries using assisted reproductive technology (ART). STUDY DESIGN: From the Birth Reporting Registry and the Assisted Reproduction Registry, we retrieved data of 4 016 530 live birth deliveries between 2001 and 2020; among them 71 000 (1.77%) were after ART. We calculated the rate of multiples and perinatal outcomes per 1000 deliveries annually from 2001 to 2020 for deliveries using and not using ART and computed the population attributable risk. We performed interrupted time series to assess the effect of the intervention, ie, the Assisted Reproduction Act. RESULTS: The proportion of deliveries following ART was 0.57% in 2001 and increased to 4.03% in 2020. After the intervention, there were decreasing trends over time for rates of multiples (-10.63 per year, P < .001), preterm delivery (-6.74, P = .003), LBW (-9.38, P < .001), and SGA (-4.48, P = .001) among ART deliveries. There was also an immediate decrease right after intervention (-53.45, P = .005) for SGA after ART. The population attributable risk trends before and after intervention were both increasing for all outcomes. CONCLUSIONS: The Assisted Reproduction Act in Taiwan was associated with a decreasing trend of multiples, preterm delivery, LBW, and SGA over time since 2008 among ART deliveries. In particular, there was an immediate decrease of SGA right after the intervention.

An ESHG-ESHRE survey on the current practice of expanded carrier screening in medically assisted reproduction.

STUDY QUESTION: What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER: The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY: The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION: Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS: The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

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.

Survey on ART and IUI: legislation, regulation, funding, and registries in European countries-an update.

STUDY QUESTION: How are ART and IUI regulated, funded, and registered in European countries, and how has the situation changed since 2018? SUMMARY ANSWER: Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding varies across and sometimes within countries (and is lacking or minimal in four countries), and national registries are in place in 33 countries; only a small number of changes were identified, most of them in the direction of improving accessibility, through increased public financial support and/or opening access to additional subgroups. WHAT IS KNOWN ALREADY: The annual reports of the European IVF-Monitoring Consortium (EIM) clearly show the existence of different approaches across Europe regarding accessibility to and efficacy of ART and IUI treatments. In a previous survey, some coherent information was gathered about how those techniques were regulated, funded, and registered in European countries, showing that diversity is the paradigm in this medical field. STUDY DESIGN, SIZE, DURATION: A survey was designed using the SurveyMonkey tool consisting of 90 questions covering several domains (legal, funding, and registry) and considering specific details on the situation of third-party donations. New questions widened the scope of the previous survey. Answers refer to the situation of countries on 31 December 2022. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: All members of the EIM were invited to participate. The received answers were checked and initial responders were asked to address unclear answers and to provide any additional information considered relevant. Tables resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, requesting a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE: Information was received from 43 out of the 45 European countries where ART and IUI are performed. There were 39 countries with specific legislation on ART, and artificial insemination was considered an ART technique in 33 of them. Accessibility is limited to infertile couples only in 8 of the 43 countries. In 5 countries, ART and IUI are permitted also for treatments of single women and all same sex couples, while a total of 33 offer treatment to single women and 19 offer treatment to female couples. Use of donated sperm is allowed in all except 2 countries, oocyte donation is allowed in 38, simultaneous donation of sperm and oocyte is allowed in 32, and embryo donation is allowed in 29 countries. Preimplantation genetic testing (PGT)-M/SR (for monogenetic disorders, structural rearrangements) is not allowed in 3 countries and PGT-A (for aneuploidy) is not allowed in 10; surrogacy is accepted in 15 countries. Except for marital/sexual situation, female age is the most frequently reported limiting criterion for legal access to ART: minimal age is usually set at 18 years and the maximum ranges from 42 to 54 with some countries not using numeric definition. Male maximum age is set in very few countries. Where third-party donors are permitted, age is frequently a limiting criterion (male maximum age ranging from 35 to 50; female maximum age from 30 to 37). Other legal restrictions in third-party donation are the number of children born from the same donor (or, in some countries, the number of families with children from the same donor) and, in 12 countries, there is a maximum number of oocyte donations. How countries deal with the anonymity is diverse: strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), a mixed system (anonymous and non-anonymous donations), and strict non-anonymity. Inquiring about donors' genetic screening showed that most countries have enforced either mandatory or scientific recommendations that exclude the most prevalent genetic diseases, although, again, diversity is evident. Reimbursement/compensation systems exist in more than 30 European countries, with around 10 describing clearly defined maximum amounts considered acceptable. Public funding systems are extremely variable. One country provides no financial assistance to ART/IUI patients and three offer only minimal support. Limits to the provision of funding are defined in the others i.e. age (female maximum age is the most used), existence of previous children, BMI, maximum number of treatments publicly supported, and techniques not entitled for funding. In a few countries reimbursement is linked to a clinical policy. The definitions of the type of expenses covered within an IVF/ICSI cycle, up to which limit, and the proportion of out-of-pocket costs for patients are also extremely dissimilar. National registries of ART are in place in 33 out of the 43 countries contributing to the survey and a registry of donors exists in 19 of them. When comparing with the results of the previous survey, the main changes are: (i) an extension of the beneficiaries of ART techniques (and IUI), evident in nine countries; (ii) public financial support exists now in Albania and Armenia; (iii) in Luxembourg, the only ART centre expanded its on-site activities; (iv) donor-conceived children are entitled to know the donor identity in six countries more than in 2018; and (v) four more countries have set a maximum number of oocyte donations. LIMITATIONS, REASONS FOR CAUTION: Although the responses were provided by well-informed and committed individuals and submitted to double checking, no formal validation by official bodies was in place. Therefore, possible inaccuracies cannot be excluded. The results presented are a cross-section in time, and ART and IUI frameworks within European countries undergo continuous modification. Finally, some domains of ART activity were deliberately left out of the scope of this survey. WIDER IMPLICATIONS OF THE FINDINGS: Our results offer a detailed updated view of the ART and IUI situation in European countries. It provides extensive answers to many relevant questions related to ART usage at the national level and could be used by institutions and policymakers at both national and European levels. STUDY FUNDING/COMPETING INTEREST(S): The study has no external funding, and all costs were covered by ESHRE. There were no competing interests.

Infertility treatments and cyanotic congenital heart defects among livebirths in the USA: findings from a contemporary cohort.

STUDY QUESTION: Is there an elevated risk of cyanotic congenital heart defects (CCHD) among livebirths following infertility treatments? SUMMARY ANSWER: In this population-based study of single livebirths, infertility treatment (either ART or non-ART) was associated with a higher prevalence of CCHD among livebirths. WHAT IS KNOWN ALREADY: The use of infertility treatment has been on the rise over the past few decades. However, there are limited studies assessing the risk of major cardiac defects following infertility treatments. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of livebirth data from the National Vital Statistics System (NVSS) was conducted, comprising of 9.6 million singleton livebirths among first-time mothers aged 15-49 years from 2016 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on infertility treatment use and CCHD was obtained from the health and medical information section of birth certificates, which was completed by healthcare staff after reviewing medical records. Logistic regression models were used to estimate odds ratios (OR) and 95% CI. Entropy balancing weighting analysis and probabilistic bias analysis were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of births following infertility treatment increased from 1.9% (27 116) to 3.1% (43 510) during the study period. Overall, there were 5287 cases of CCHD resulting in a prevalence of 0.6 per 1000 livebirths. The prevalence was 1.2 per 1000 live births among infertility treatment users (ART: 1.1 per 1000 livebirths; non-ART: 1.3 per 1000 livebirths) while that for naturally conceived births was 0.5 per 1000 livebirths. Compared to naturally conceived births, the use of any infertility treatment (OR: 2.06, 95% CI: 1.82-2.33), either ART (OR: 2.02, 95% CI: 1.73-2.36) or other infertility treatments (OR: 2.12, 95% CI: 1.74-2.33), was associated with higher odds of CCHD after adjusting for maternal and paternal age, race and ethnicity, and education, as well as maternal nativity, marital status, source of payment, smoking status, and pre-pregnancy measures of BMI, hypertension and diabetes. This association did not differ by the type of infertility treatment (ART versus other infertility treatments) (OR: 1.04, 95% CI: 0.82-1.33, P = 0.712), and was robust to the presence of exposure and outcome misclassification bias and residual confounding. LIMITATIONS, REASONS FOR CAUTION: The findings are only limited to livebirths. We did not have the capacity to examine termination data, but differential termination by mode of conception has not been supported by previous studies designed to consider it. Infertility treatment use was self-reported, leading to the potential for selection bias and misclassification for infertility treatment and CCHD. However, the association persisted when systematic bias as well as exposure and outcome misclassification bias were accounted for in the analyses. Information on the underlying etiology of infertility relating to either maternal, paternal, or both factors, data on specific types of ART and other infertility treatments, as well as information on subtypes of CCHD, were all not available. WIDER IMPLICATIONS OF THE FINDINGS: In light of the increasing trend in the use of infertility treatment in the USA, and elsewhere, the finding of the current study holds significant importance for the clinical and public health of reproductive-aged individuals. The data show that the use of infertility treatment may expose offspring to elevated odds of severe congenital heart defects such as CCHD studied here. These findings cannot be interpreted causally. While our findings can assist in preconception counseling and prenatal care for pregnancies conceived by either ART or other infertility treatments, they also support some current recommendations that pregnancies resulting from infertility treatments undergo fetal echocardiography screening. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for the study. The authors declare that they have no conflict of interest. TRIAL REGISTRAION NUMBER: N/A.

Obstetric outcomes of nulliparous women with pelvic pain undergoing fertility treatment.

RESEARCH QUESTION: Is there any association between pelvic pain and primary caesarean delivery for patients undergoing assisted reproductive technology (ART) treatment? DESIGN: Retrospective cohort study of nulliparous patients with singleton pregnancies who underwent ART treatment and achieved a live birth between 2012 and 2020. Cases included patients diagnosed with pelvic pain. A 3:1 ratio propensity-score-matched population of patients without a history of pelvic pain was included as the control group. Comparative statistics were performed using chi-squared test and Student's t-test. A multivariate regression analysis was conducted to evaluate the association between pelvic pain and mode of delivery. RESULTS: One hundred and seventy-four patients with pelvic pain were compared with 575 controls. Patients with pelvic pain reported a significantly longer duration of infertility compared with controls (18.98 ± 20.2 months versus 14.06 ± 14.06 months; P = 0.003). Patients with pelvic pain had a significantly higher rate of anxiety disorders (115 ± 21.9 versus 55 ± 31.6; P = 0.009) and use of anxiolytics at embryo transfer (17 ± 3.2 versus 12 ± 6.9; P = 0.03) compared with controls. In addition, patients with pelvic pain had a higher rate of primary caesarean delivery compared with controls (59.8% versus 49.0%; P = 0.01). After adjusting for multiple variables, a significant association was found between pelvic pain and increased odds of primary caesarean delivery (adjusted OR 1.48, 95% CI 1.02-2.1). CONCLUSION: Patients with pelvic pain have significantly higher odds of primary caesarean delivery compared with patients without a history of pelvic pain. The infertility outpatient setting may be uniquely positioned to identify patients at risk for undergoing primary caesarean delivery, and could facilitate earlier intervention for pelvic floor physical therapy during the preconception and antepartum periods.

Impact of body mass index on assisted reproductive technology outcomes in patients with polycystic ovary syndrome: a meta-analysis.

The effect of obesity on pregnancy outcomes of patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART) remains unclear. As such, a meta-analysis of recent studies was conducted to probe the effect of being overweight or obese on ART pregnancy outcomes in patients with PCOS. PubMed, Embase, MEDLINE, Scopus and Web of Science were searched from inception to 22 July 2023 without language restrictions. The main indicators were: live birth rate, clinical pregnancy rate, spontaneous abortion rate and multiple pregnancy rate. Ten studies were analysed, with a combined sample size of 247,845. Among patients with PCOS undergoing ART who were overweight or obese, the live birth rate, clinical pregnancy rate, implantation rate and number of retrieved oocytes were lower than in normal-weight patients with PCOS, and the spontaneous abortion rate was higher than in normal-weight patients with PCOS. Obese patients with PCOS undergoing ART had a lower multiple pregnancy rate and a lower number of mature oocytes compared with normal-weight patients with PCOS. The data showed that, among patients with PCOS, being overweight or obese has a negative effect on ART pregnancy outcomes. This meta-analysis may inform guidelines for pregnancy with ART, and encourage overweight or obese patients with PCOS to lose weight.

Is infertility more common among patients with multiple sclerosis? Implications for utilization of assisted reproductive techniques.

RESEARCH QUESTION: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)? DESIGN: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyse the association between multiple sclerosis and fertility treatments including IVF and ovarian stimulation. RESULTS: During the study period, 1309 multiple sclerosis patients were compared with 13,090 controls from the general population matched for age. The mean age was 29 ± 7.8 years. The overall prevalence of infertility was 15.4% (202/1309) among the multiple sclerosis patients, similar to the general population (16.3%; 2129/13090) (P = 0.436). The prevalence of IVF and ovarian stimulation was similar among multiple sclerosis patients and matched controls from the general population (8.1% versus 7.2%, P = 0.240; 13.8% versus 14.3%; P = 0.624, respectively). CONCLUSIONS: The results show similar rates of infertility and fertility treatments among multiple sclerosis patients and the general population. This provides reassurance that fertility among women with multiple sclerosis does not differ from that of women in the general population, and indicates there is no excessive usage of ART.

Pregnancy and infertility in orthopedics: A review of the current state.

BACKGROUND: Orthopedic surgery continues to have one of the lowest rates of female trainees among all medical specialties in the United States. Barriers to pursuing a surgical residency include the challenges of family planning and work-life balance during training. METHODS: A systematic literature search of articles published between June 2012 and December 2022 in the MEDLINE, EMBASE, and Cochrane databases was performed in January 2023 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Studies were included if they evaluated pregnancy and peripartum experience and/or outcomes amongst orthopedic surgeons or trainees. RESULTS: Eighteen studies were included. Up to 67.3% of female orthopedic surgeons and trainees and 38.7% of their male counterparts delayed childbearing during residency. The most reported reasons for this delay included career choice as an orthopedic surgeon, residency training, and reputational concerns among faculty or co-residents. Infertility ranged from 17.0% to 30.4% in female orthopedic surgeons and up to 31.2% suffered obstetric complications. Assisted Reproductive Technology (ART) resulted in 12.4%-56.3% of successful pregnancies. Maternity and paternity leaves ranged from 1 to 11 weeks for trainees with more negative attitudes associated with maternal leave. CONCLUSIONS: Female orthopedic trainees and attending delay childbearing, experience higher rates of obstetric complications, and more stigma associated with pregnancy compared to their male colleagues. Program and institutional policies regarding maternity and paternity leave are variable across programs, and therefore, attention should be directed toward standardizing policies.

Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.

OBJECTIVE: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally. METHODS: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally. RESULT: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05). CONCLUSION: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.

Gestational diabetes mellitus in patients undergoing assisted reproductive techniques or conceiving spontaneously: an analysis on maternal and foetal outcomes.

PURPOSE: With the rise of medically assisted reproductive techniques (ART) the number of pregnancies complicated by gestational diabetes mellitus (GDM) has increased. The aim of this study was to evaluate retrospectively the outcomes of pregnancies complicated by GDM who conceive trough ART (cases) compared to those who conceived spontaneously (controls). METHODS: In 670 women with GDM, 229 cases and 441 controls, followed by the Diabetology of Padua, between 2010-2022, clinical-metabolic maternal characteristics and maternal-foetal outcomes were evaluated. RESULTS: As for the maternal clinical-metabolic characteristics, plasma glucose levels at 60' and 120' under oral glucose tolerance test (OGTT) at time of diagnosis were significantly higher in cases (177.4 ± 31.1 vs 170.9 ± 34.1 mg/dl, p = 0.016; 151.5 ± 32.2 vs 144.0 ± 33.4 mg/dl, p = 0.005 respectively). Furthermore, at diagnosis, cases show higher levels of total cholesterol (257 ± 53 mg/dl vs 246 ± 52 mg/dl; p = 0.012) and triglycerides (199.8 ± 83.2 mg/dl vs 184.9 ± 71.3 mg/dl; p = 0.02) compared to controls. As for maternal outcomes, thyroid disfunction, was recorded in a higher percentage in case (21.4% vs 14.3%; p = 0.008), as well as, the frequency of cesarean section (50.3% vs 41.2%; p = 0.038) and twin pregnancies (16.2% vs 2.5%; p < 0.001). As for neonatal outcomes, there were no statistically significant differences, except for the birth weight of the second twin, which was significantly lower in cases (2268 ± 536 vs 2822 ± 297 g; p = 0.002). No other significant differences were found. CONCLUSION: This study showed no meaningful differences in the outcomes of GDM pregnancies who were conceived with ART compared to that arose spontaneously as the patients were promptly diagnosed and treated.

Violence and its related factors among infertile women attending assisted reproductive technique unit at Al-Azhar University, Cairo.

BACKGROUND: Violence against women is a distressing issue particularly when they are infertile. Nevertheless, many women who are infertile and exposed to violence continue their marriage and justify such choice. AIM: The current study aimed to assess the prevalence of violence against infertile women and its associated factors. PARTICIPANTS AND METHODS: This cross-sectional study involved 364 Egyptian women with primary infertility; they were randomly selected from the assisted reproductive technique unit of Al-Azhar University's International Islamic Center for Population Studies and Research. The data were collected through an interview questionnaire including the Infertile Women's Exposure to Violence Determination Scale (IWEVDS), socio-demographic, conception, and community-related factors. RESULTS: Moderate/high violence level was detected among 50.5% (95% CI = 45.3- 55.8%) of the studied infertile women, the mean ± SD of total score of IWEVDS was 48.27 ± 21.6. Exclusion was the most frequent type of violence among them. Binary logistic regression revealed that wives who had lower-educated husbands, lived in low-income families, had undergone prior IVF treatment, and who perceived gender inequality acceptance in society were more likely to expose to violence than others (OR = 3.76, 4.25, 2.05, and 2.08 respectively) (P value < 0.05). CONCLUSION AND RECOMMENDATIONS: Infertile women have frequent exposure to different types of violence and many factors were implicated in such condition. Despite exposure to violence, infertile women refused divorce because they had no alternative financial sources as well as they were afraid of loneliness. A community mobilization approach to control this problem through a collaboration of all stakeholders is recommended.

Assessment of embryologist sufficiency and associated regional disparities in Japanese assisted reproduction facilities using nationwide survey data (IZANAMI project).

AIMS: This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). METHODS: A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. RESULTS: The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. CONCLUSION: In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

Variation in diagnostic methods, criteria, and treatment for chronic endometritis: A nationwide survey in Japan.

AIM: To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. METHODS: We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first- and second-line treatment protocols for CE were collected via a questionnaire. RESULTS: Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138-positive cells for diagnosing CE was 3-5 cells/20 high-power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first- and second-line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. CONCLUSIONS: There is considerable variation in the number of CD138-positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

Mitigating multiples, less is more: examining trends in multifetal gestation rates with assisted reproductive technology.

PURPOSE: Multifetal gestation (MFG) is much more common in pregnancies that utilize assisted reproductive technologies (ART). We assessed how these rates have changed over the previous decade and the impact on live birth rates (LBR). METHODS: This retrospective cohort study uses the National Summary Reports of the Society for Assisted Reproductive Technology (SART) from 2014 to 2020. Data points included only autologous cycles. The data were divided into five age groups as reported in the database: < 35, 35-37, 38-40, 41-42, and > 42 years old. Descriptive statistics and a two-tailed T-test were used to determine the trends and statistical significance (p < 0.05). RESULTS: Rates of twin births decreased substantially from 2014 to 2020 for autologous embryo transfers across all age groups and diagnoses. Surprisingly, the overall LBR for autologous IVF cycles decreased at similar rates from 2014 to 2020 in all age groups. The mean number of embryos transferred has dramatically reduced, especially across age groups < 42. CONCLUSION: Rates of twin and higher-level gestations have decreased substantially over the past decade; the effect correlates with the increased utilization of eSET and PGT. The cause of infertility did not significantly impact the rate of MFG.

Pregnancy outcomes after assisted reproductive technology among women with endometriosis in Ukraine: results a multicenter study.

OBJECTIVE: Aim: To evaluate the association between adverse pregnancy outcome, assisted reproductive technology (ART) and a previous diagnosis of endometriosis in Ukraine. PATIENTS AND METHODS: Materials and Methods: We conducted a multicentre retrospective cohort study was based on infertility surveillance data among women reproductive age from January 1st, 2017 to December 31st, 2021 in Ukraine. The patients from 10 Ukrainian regions who achieved singleton pregnancy by ART were included in this study. Linked hospital, pregnancy/birth and mortality data were used. Logistic regression analysis was performed to calculate odds ratios (OR) and 95 % confidence interval (CI) for the rates of adverse pregnancy outcomes. RESULTS: Results: During study period within the cohort of 11,271 singleton births, 94 women with endometriosis diagnosed before birth delivered 102 infants. Compared with women without endometriosis, women with endometriosis had higher risks of preterm birth [adjusted odds ratio 1.33, 95% confidence interval (CI), 1.23-1.44]. Women with endometriosis had higher risks of antepartal bleeding/placental complications, pre-eclampsia and Caesarean section. There was no association between endometriosis and risk of SGA-birth or stillbirth. CONCLUSION: Conclusions: Endometriosis and ART use are both independently associated with increased risk of preterm birth, antepartum haemorrhage, placenta praevia and planned birth. These findings are clinically relevant to obstetricians for distinguishing high- and low-risk pregnancies. Pregnant women with endometriosis require increased antenatal surveillance.

[The impact of health of mothers on health of children delivered by women 35-45 age old after application of auxiliary reproductive technologies].

The treatment of women aged 35 years and older with infertility applies assisted reproductive technologies (ART) in every third case. The purpose of the study is to analyze impact of maternal health on health of children who were delivered by women aged 35 years and older after application of ART. The analytical, direct observation, sociological (questioning), and statistical methods were applied. To study health status of children born after application of ART methods in women aged 35-45 years, representative main group of 648 preschool children (4-6 years old) was selected. The second control group included 649 preschool children (4-6 years old), who were as identical as possible to children from the main group, selected according to following characteristics: mother's age at birth of child (35-45 years), age (from 4 to 6 years), all were observed in same medical organization, birth from a singleton, full-term (37 weeks or more) pregnancy. The main and control groups differed from each other only in presence or absence of ART methods. The children born preterm, from egg donor programs and multiple pregnancies were excluded from study. The children health was studied according to medical examinations, medical records, child development history, and mothers questionnaire data on children health. The course of pregnancy and childbirth, morbidity and lifestyle characteristics of mothers were studied according to their questionnaires and copies of data from their outpatient medical records. It was established that there is direct correlation between health of child and health of mother (r = 0.571; p < 0.01, t = 3). At that, it was revealed that differences in level of general morbidity of children after ART and children from spontaneous pregnancy are achieved within account of significant differences in subgroup of children of mothers aged 38-45 years (3353.7‰ and 2341.8‰ control group).

Model-based estimation of the health care expenditure and out-of-pocket payment for assisted reproductive technology: A retrospective linkage study using the Japanese national ART registry.

AIM: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. METHODS: We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. RESULTS: We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). CONCLUSIONS: Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.