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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., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications., Methods: Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student's t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type., Results: A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P < 0.05). The cumulative live birth rate of the gynecologic cancer group was significantly lower than that of the control group (36.10% vs. 60.50%, P < 0.001). Maternal and neonatal complications did not significantly differ between the groups (P > 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P < 0.001, respectively)., Conclusions: These findings highlight the decreased occurrence of pregnancy and live birth in female gynecologic cancer patients undergoing ART, particularly in endometrial cancers and cervical cancers. These findings have important implications for counseling and managing gynecologic cancer patients undergoing ART., (© 2024. The Author(s).)

Infertility disproportionately affects the minority, non-White populace, with Black women having twofold higher odds than White women. Despite higher infertility rates, minority racial and ethnic groups access and utilize fertility care less frequently. Even once care is accessed, racial and ethnic disparities exist in infertility treatment and ART outcomes. Preliminary studies indicate that Asian and American Indian women have lower intrauterine insemination pregnancy rates. Many robust studies indicate significant racial and ethnic disparities in rates of clinical pregnancy, live birth, pregnancy loss, and obstetrical complications following in vitro fertilization, with lower favorable outcomes in Black, Asian, and Hispanic women., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate hospitalizations up to 8 years after live birth among women who used assisted reproductive technology (ART) or who were subfertile compared with women who conceived naturally., Design: Retrospective cohort., Setting: Deliveries among privately insured women aged ≥18 years between 2004 and 2017 from Massachusetts state vital records were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and hospital observational/inpatient stays., Patient(s): We compared patients with ART, medically assisted reproduction (MAR), and unassisted subfertile (USF) delivery with those with fertile delivery., Intervention(s): NA., Main Outcome Measure(s): Postdelivery hospitalization information was derived from the International Classification of Diseases codes for discharges and combined by type. The relative risks and 95% confidence intervals (CIs) of hospitalization for up to the first 8 years postdelivery were modeled., Result(s): Among 492,515 deliveries, 5.6% used ART, 1.6% used MAR, and 1.8% were USF. Compared with fertile deliveries, deliveries that used ART or MAR or were USF were more likely to have hospital utilization (inpatient or observational stay) for any reason for up to 8 years of follow-up (USF, adjusted relative risk [aRR], 1.18 [95% CI, 1.12-1.25]; MAR, aRR, 1.20 [1.13-1.27]; and ART, aRR, 1.29 [1.25-1.34]). Assisted reproductive technology deliveries had an increased risk of hospitalization for conditions of the cardiovascular system (aRR, 1.31 [95% CI, 1.20-1.41]), overweight/obesity (aRR, 1.30 [1.17-1.44]), diabetes (aRR, 1.25 [1.05-1.49]), reproductive tract (aRR, 1.62 [1.47-1.79]), digestive tract (aRR, 1.39 [1.30-1.49]), thyroid (aRR, 2.02 [1.80-2.26]), respiratory system (aRR, 1.13 [1.03-1.24]), and cancer (aRR, 1.40 [1.18-1.65]) up to 8 years after delivery. Deliveries with MAR and subfertility had similar patterns of hospitalization as ART deliveries., Conclusion(s): Women who conceived through fertility treatment or experienced subfertility were at increased risk of subsequent hospitalization resulting from a variety of chronic and acute conditions., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time., Design: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013., Setting: Seventy-five countries and 2,639 ART clinics., Patient(s): Women and men undergoing ART procedures., Intervention(s): All ART., Main Outcome Measure(s): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART)., Result(s): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed., Conclusion(s): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify risk factors for severe psychological stress in women undergoing fertility treatment., Methods: This cross-sectional, multi-center study was conducted from August to December 2018. We recruited 1672 subjects who completed an anonymous, self-reported questionnaire regarding fertility treatment, conditions at work and home, and psychological stress using K6 score, which estimates psychological distress during the previous 30 days. We further focused our analysis on 1335 subjects who were working when starting fertility treatment., Results: Of 1672 women, mean K6 score (range 0-24) was 4.8 ± 4.4, including 103 women (6.2%) with K6 score ≥ 13 (high K6), and classified as probable severe psychological distress. Multivariate logistic regression analysis showed that high K6 was strongly associated with low annual family income of ≤ USD55,700 (JPY6 million) (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.04-3.42), infertility duration of ≥ 2 years (OR 1.87, 95% CI 1.08-3.25), and no experience of childbirth (OR 2.04, 95% CI 1.05-3.97). Focusing on 1335 working women, 266 (19.9%) experienced resignation from work. High K6 was strongly associated with low family income (OR 2.83, 95% CI 1.52-5.28), cessation of professional duties (OR 2.08, 95% CI 1.05-4.14), infertility-related harassment in the workplace (OR 2.07, 95% CI 1.08-3.98), and perceived difficulties to continue working during fertility treatment (OR 2.94, 95% CI 1.15-7.50)., Conclusion: Severe psychological stressors in women during fertility treatment included low family income, long infertility duration, childlessness, infertility-related harassment, and perceived difficulty in working conditions or cessation from work. Establishment of mental health care support systems is urgently required in this population.

Background: This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f ® ) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP ® ), during assisted reproductive technology (ART) treatments in Germany., Methods: Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle)., Results: Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP., Conclusions: This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.

Purpose: We previously developed a subfertile comparison group with which to compare outcomes of assisted reproductive technology (ART) treatment. In this study, we evaluated whether insurance claims data in the Massachusetts All Payers Claims Database (APCD) defined a more appropriate comparison group., Methods: We used Massachusetts vital records of women who delivered between 2013 and 2017 on whom APCD data were available. ART deliveries were those linked to a national ART database. Deliveries were subfertile if fertility treatment was marked on the birth certificate, had prior hospitalization with ICD code for infertility, or prior fertility treatment. An infertile group included women with an APCD outpatient or inpatient ICD 9/10 infertility code prior to delivery. Fertile deliveries were none of the above. Demographics, health risks, and obstetric outcomes were compared among groups. Multivariable generalized estimating equations were used to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI)., Results: There were 70,726 fertile, 4,763 subfertile, 11,970 infertile, and 7,689 ART-treated deliveries. Only 3,297 deliveries were identified as both subfertile and infertile. Both subfertile and infertile were older, and had more education, chronic hypertension, and diabetes than the fertile group and less than the ART-treated group. Prematurity (aRR = 1.15-1.17) and birthweight (aRR = 1.10-1.21) were increased in all groups compared with the fertile group., Conclusion: Although the APCD allowed identification of more women than the previously defined subfertile categorization and allowed us to remove previously unidentified infertile women from the fertile group, it is not clear that it offered a clinically significantly improved comparison group.

Background: Poor ovarian response to gonadotropin is a significant challenge in assisted reproductive technique (ART) and affect 9-24% of ART cycles. This study aimed to evaluate the effect of Myo-inositol on fertility rates in poor ovarian responder women undergoing assisted reproductive technique., Methods: This study is a double-blinded randomized controlled study that involved 60 poor ovarian responders included in an ICSI program and divided into two groups; intervention group: 30 patients who have been assuming Inofolic (4 g myo-inositol + 400 μg folic acid) for the before the enrollment day; control group: 30 patients assuming folic acid (400 μg) for the same period. Controlled ovarian stimulation was performed in the same manner in the two groups. The main outcomeswere the assessment of oocytes retrievednumber and quality, ovarian sensitivity index,required dose of Gonadotropinsunits × 1000), fertilization rate, biochemical, and clinical pregnancy rate., Result: There is no significant difference in clinical characteristics between study groups. The number of oocytes retrieved, number of MII oocytes, number of embryos transferred, chemical, and clinical pregnancy were higher in the intervention group. However, they are not statistically significant in comparison to the control group. The ovarian sensitivity index and fertilization rate were significantly higher in the intervention group than the control group (P > 0.05). The required dose of gonadotropin significantly lower in the intervention group than the control group., Conclusion: Our results suggest that the supplementation myo-inositol in poor ovarian responders significantly improved the ART outcomes such as fertilization rate gonadotropin, ovarian sensitivity index (OSI) and significantly reduced the required unities of gonadotropin. Additionally, more extensive randomized controlled studies are needed., Trial Registration: Iranian Registry of Clinical Trials, IRCT20180515039668N1 , retrospectively registered since 2020-03-16.

The Danish National Register of assisted reproductive technology (ART) was initially established in 1994. The register comprises complete information on all ART procedures in public and private clinics in Denmark from 2013 and onwards, including baseline information on the cause of infertility and a number of health-related patient characteristics. The register enables monitoring and research on infertility treatment and reproductive topics in single women or couples seeking assisted reproduction, and the register is thus a key component of the Danish health information system within human reproduction. We aimed to provide an updated description of the register including advantages and pitfalls when using the register for reproductive epidemiological research, and a description of the accessibility for researchers. The Danish ART register is a valuable tool for epidemiological research. However, the inherent strengths and limitations ought to be in perspective when designing studies and interpreting the study results. Reports with annually aggregated data on ART treatments, can be accessed on the Danish Health Data Authority web page and researchers may obtain access to individual pseudonomized data via secure servers at the Danish Health Data Authority and Statistics Denmark.

Objective: To evaluate the assisted reproductive technology (ART) cumulative live-birth rate (LBR) in a cohort of bowel endometriosis patients with no prior history of surgery for endometriosis., Design: Prospective cohort study., Setting: University hospital., Patient(s): One hundred and one consecutive infertile bowel-endometriosis patients with no prior history of surgery for endometriosis in whom the diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging., Intervention(s): First-line ART., Main Outcome Measure(s): Cumulative LBR, with statistical analysis via Kaplan Meier method with a "conservative" method, whereby it was assumed that no live births took place for patients who did not return., Result(s): Between January 2016 and December 2018, 101 bowel endometriosis patients underwent 176 ART cycles. The mean number of deep-infiltrating endometriosis lesions per patient was 3 ± 0.9, with a mean number of bowel lesions of 1.3 ± 0.6. Seventy-three percent of the patients had associated endometriomas, and 88.1% had associated adenomyosis. Overall, the cumulative LBR after four ART cycles was 64.4%, using the conservative Kaplan-Meier method., Conclusion(s): The ART cumulative LBR was very satisfactory (64.4%) in bowel endometriosis patients with no prior history of surgery for endometriosis. In light of these data, clinicians should carefully weigh the pros and cons before systematically referring infertile bowel endometriosis patients to fertility-preserving surgery because as first-line ART appears to offer satisfactory results., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There has been an interest in the relationship between ABO blood groups and infertility. Many studies have investigated the association of ABO blood groups with diminished ovarian reserve (DOR), ovarian hyperstimulation syndrome (OHSS), and outcomes of assisted reproductive technology (ART), with controversial results., Methods: A systematic review and meta-analysis was conducted to evaluating the association of ABO blood groups with DOR, OHSS, and outcomes of ART., Results: Thirteen studies performed between 2010 and 2018 were included in this meta-analysis. DOR, OHSS, live birth rate (LBR), clinical pregnancy rate (CPR), miscarriage rate (MR) were reported in 9, 2, 4, 3, 2 studies, respectively. The combined results showed similar risk of DOR among individuals with blood group A (RR, 0.98; 95% confidence interval [CI], 0.85, 1.13), B (RR, 0.96; 95% CI, 0.76, 1.20), AB (RR, 1.00; 95% CI, 0.76, 1.30), and non-O (RR, 0.94; 95% CI, 0.79, 1.11) as compared to those with blood group O. Meta-analysis showed that the incidences of OHSS were similar in women with blood group A (RR, 1.05; 95% CI, 0.66, 1.66), B (RR, 1.04; 95% CI, 0.46, 2.35), AB (RR, 0.51; 95% CI, 0.10, 2.56), non-O (RR, 1.02; 95% CI, 0.65, 1.57) with blood group O. As to the clinical outcomes, meta-analysis showed no difference in LBR among individuals with blood group A (RR, 1.27; 95% CI, 0.74, 2.17), B (RR, 1.47; 95% CI, 0.95, 2.29), AB (RR, 1.48; 95% CI, 0.76, 2.90), non-O (RR, 1.28; 95% CI, 0.83, 1.98) when compared to those with blood group O. Similarly, the results also found that there were no difference in CPR and MR between women with blood A (CPR: RR, 1.12), B (CPR: RR, 1.08), AB (CPR: RR, 1.05), non-O (CPR: RR, 1.05; MR: RR, 0.94) and blood group O., Conclusions: ABO blood groups may not be associated with DOR, OHSS, LBR, CPR, and MR of ART. Infertility and ART outcomes are influenced by multiple factors. Blood groups should not be taken into account excessively during diagnosis and treatment of infertile women.

Background: What are the trends and figures in the treatments involving Assisted Reproductive Technology (ART) in mainland China? Method: The Chinese Society of Reproductive Medicine (CSRM) retrospectively collected and analyzed data from 2013 to 2016 in 28 province of China by CSRM ART Data Reporting System. Results: Among the 327 centers in China by December 2016, 133 centers reported 1,211,303 cycles and 470,725 infants in the 4 year period. Since 2013, the total number of frozen embryo transfer (FET) cycles, PGD/PGS cycle showed an increasing trend year by year. However, the number of donor sperm (DS) and donor egg (DE) cycles remained at a low level. Pregnancy outcomes such as implantation rate, pregnancy rate and delivery rate per embryo transfer cycles were stable in all types of ART, but decreased dramatically with increasing age. However, the average number of transferred embryos gradually decreased from 2013 to 2016, especially in PGD/PGS cycles. Thus, multiple pregnancy rate also decreased, it decreased significantly in PGD/PGS cycles from 30.5% in 2013 to only 1.7% in 2016. Conclusions: The current study gives valuable information for both physicians and patients to know better about the outcome, as well as for administrators for policy development., (Copyright © 2020 Hu, Bu, Huang, Sun, Deng and Sun.)

Objectives. To measure trends in infertility treatment use between 2008 and 2017 in France using data from the national health insurance system. Methods. Between 2008 and 2017, we observed a representative national sample of nearly 1% of all women aged 20 to 49 years who were affiliated with the main health insurance scheme in France (more than 100 000 women observed each year). We exhaustively recorded all health care reimbursed to these women. Results. Among women aged 20 to 49 years, 1.25% were treated for infertility each year. Logistic regression analysis showed a significant interaction between age and year of treatment use ( P  < .001). Over the decade, infertility treatment use increased by 23.9% among women aged 34 years or older, whereas among women younger than 34 years there was a nonsignificant variation. Conclusions. Women aged 34 years or older were increasingly treated for infertility between 2008 and 2017. Public Health Implications. Treatment efficiency decreases strongly with a woman's age, presenting a challenge for medical infertility care.

Thyroid autoimmunity (TAI) and/or thyroid dysfunction are prevalent in women of reproductive age and have independently been associated with adverse fertility and pregnancy outcomes, in the case of spontaneous conception or after assisted reproductive technology (ART). Thus, it seems reasonable to screen for thyrotropin (TSH) and thyroid peroxidase autoantibodies (TPO-abs) in infertile women attempting pregnancy. However, even if the relationship between fertility and thyroid dysfunction and/or TAI persists when properly controlled for other variables, it remains challenging to claim causation. Several studies with different designs (cross sectional, case -control, prospective and retrospective cohort studies) have looked at the association between thyroid autoimmunity, thyroid function and fertility. Heterogeneity among study results are related to small numbers of included patients, poor study design, selection of causes of infertility and different assays used to measure TAI, thyroid hormones and TSH reference values. Indeed, there is no consensus regarding the upper limit of normal for TSH to define thyroid dysfunction and the cut-off levels for intervention. Furthermore, data from interventional trials looking at the impact of levothyroxine treatment on fertility outcome in randomised controlled studies are scarce. Despite the recent update of the guidelines by the American Thyroid Association (ATA) for the Diagnosis and Management of Thyroid Disease during Pregnancy and the postpartum, many questions remain unsettled in ART., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the risk of abnormal perinatal outcomes in young patients with diminished ovarian reserve (DOR)., Design: A retrospective cohort study., Setting: Reproductive medicine center in a hospital., Patients: A total of 5,649 young patients (≤35 years) undergoing assisted reproductive technology for fresh-cycle ET between January 1, 2016, and January 31, 2019, were included. The patients were divided into two groups: the non-DOR group (n = 5,295) and the DOR group (n = 354)., Intervention(s): None., Main Outcome Measure(s): Singleton live births were assessed for obstetrical complications and adverse birth outcomes., Result(s): There were significantly lower rates of clinical pregnancy, live birth, and singleton live birth among young patients with DOR, without an increase in the rates of clinical pregnancy loss, biochemical pregnancy, and multiple live births compared with young patients without DOR. For young patients with singleton live births, there were no significant differences in the incidence of gestational hypertension, gestational diabetes mellitus, placenta previa, fetal malformation, macrosomia, low birth weight, or preterm birth between the two groups after adjusting with a multiple logistic regression model., Conclusion(s): We found that young patients with DOR still had acceptable pregnancy outcomes and similar risks of biochemical pregnancy, pregnancy loss, multiple live births, and abnormal perinatal outcomes compared with young patients with normal ovarian reserve., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the impact of a 3-month course of intracortical injections of autologous platelet-rich plasma (PRP) upon ovarian reserve markers versus no intervention in women with low ovarian reserve prior to undergoing assisted reproductive technology (ART)., Methods: Prospective controlled, non-randomized comparative study conducted in a private fertility clinic, in Venezuela. Women with abnormal ovarian reserve markers (FSH, AMH and AFC) who declined oocyte donation were allocated to one of the following groups according to patient choice: monthly intracortical ovarian PRP injections for three cycles, or no intervention. Primary outcomes were the change in FSH, AMH and AFC pre- and post-treatment. Secondary outcomes included the number of oocytes collected and fertilized, biochemical/clinical pregnancy rates and miscarriage and live birth rates., Results: Eighty-three women were included, of which 46 received PRP treatment and 37 underwent no intervention. Overall median age was 41 years (IQR 39-44). There were no demographic differences between the study groups. At the 3-month follow-up, women treated with PRP experienced a significant improvement in FSH, AMH and AFC, whereas there was no change in the control group. Furthermore, overall rates of biochemical (26.1% versus 5.4%, P = 0.02) and clinical pregnancy (23.9% versus 5.4%, P = 0.03) were higher in the PRP group, while there was no difference in the rates of first trimester miscarriage and live birth between groups., Conclusion: PRP injections are effective and safe to improve markers of low ovarian reserve prior to ART, although further evidence is required to evaluate the impact of PRP on pregnancy outcomes.

Background: Studies have shown that fertility treatment in mothers is associated with neurological problems in children. However, knowledge about any association between maternal use of fertility treatment and febrile seizures in children is lacking., Objective: To determine whether maternal use of fertility treatment is associated with febrile seizures in children., Methods: All liveborn children in Denmark during 1996-2012 (n = 1 065 901) were linked with the Danish Infertility Cohort and the Danish national registers and were followed from one year of age until the first episode of a febrile seizure, death, emigration, loss to follow-up, or end of follow-up (December 2015). Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders., Results: Approximately 16% children (n = 172 140) were conceived by infertile women, and approximately 3% (n = 34 082) were diagnosed with febrile seizures during follow-up. Compared with children conceived by fertile women, children conceived following any fertility treatment (HR 1.11, 95% CI 1.06, 1.16), following specific fertility treatment, for example IVF (HR 1.15, 95% CI 1.05, 1.25), ICSI (HR 1.20, 95% CI 1.10, 1.32), and following fertility drugs (HR 1.06, 95% CI 1.00, 1.11) had slight increase in risk of febrile seizures, after adjusting for calendar year of birth, parental age, education, parity status, and maternal smoking during pregnancy. The associations were unchanged when children conceived naturally by infertile women were used as the reference group., Conclusions: Children conceived following fertility treatment had slightly increased relative risk for febrile seizures., (© 2020 John Wiley & Sons Ltd.)

Objective: To determine whether biochemical or clinical markers of androgenic activity predict live birth rate with ovarian stimulation in the unexplained infertility population., Design: Secondary analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial., Setting: Multicenter university-based clinical practices., Patient(s): Nine hundred couples with unexplained infertility were included. Women were 18-40 years old with regular menses, a normal uterine cavity, at least one patent fallopian tube, and a male partner with ≥5 million motile sperm. Women were randomized to receive gonadotropin, clomiphene, or letrozole with IUI for four or fewer four treatment cycles. Women were evaluated for biochemical (total testosterone, DHEAS, and free androgen index) and clinical markers of androgenic activity (sebum, acne, and hirsutism). Multivariable logistic regression models adjusting for treatment group, maternal age, and body mass index were performed., Intervention(s): None., Main Outcome Measure(s): The primary outcome was live birth. Secondary outcomes included conception, clinical pregnancy, and pregnancy loss., Result(s): When comparing 900 women in the AMIGOS trial based on quartiles of serum TT, women were of younger age, higher body mass index, and higher waist circumference with increasing TT. Increasing quartiles of TT also showed increasing DHEAS and free androgen index values. Serum androgens were not associated with outcomes of live birth, conception, clinical pregnancy, or pregnancy loss. Clinical androgen markers were not associated with pregnancy outcomes., Conclusion(s): In a randomized cohort of women with unexplained infertility, biochemical and clinical measures of androgens did not predict live birth rate after ovarian stimulation treatment., Clinical Trial Registration Number: NCT 01044862., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: To clarify gender differences in the demographic variables and infertility problems associated with depression among men and women undergoing infertility treatment., Design: A cross-sectional study., Methods: We surveyed 380 women and 360 men undergoing infertility treatment at the reproductive medicine center of a hospital in China's Ningxia Province from March - September 2016., Results: For women, ethnicity, the number of clinic visits, social concern, and sexual concern were factors linked with depression symptoms. For men, treatment cost pressure and social concern were significantly associated with depression symptoms., Conclusion: Psychological counseling and intervention programs should be integrated into in-vitro fertilization treatments and interventions should be targeted based on gender differences., Impact: The provision of treatment-related sexual knowledge by nurses is indispensable for infertile participants. Mental health policies should be developed to facilitate the implementation of psychological services. Psychological counseling and intervention programs should be integrated into in vitro fertilization treatment to help men and women with infertility cope with psychological distress., (© 2019 John Wiley & Sons Ltd.)

Purpose: To explore the attitudes of reproductive endocrinology and infertility (REI) and maternal-fetal medicine (MFM) subspecialists regarding the necessity and appropriateness of body mass index (BMI) cutoffs for women seeking fertility treatment., Methods: Members of the Society for Reproductive Endocrinology and Infertility (SREI) and the Society for Maternal Fetal Medicine (SMFM) were invited to participate in a survey querying their knowledge of existing institutional or clinic BMI policies and personal opinions regarding upper and lower BMI cutoffs for a range of fertility treatments, including oral ovulation agents, gonadotropins, and in vitro fertilization., Results: Respondents included 398 MFMs and 201 REIs. The majority of REI and MFM providers agreed with upper limit BMI cutoffs (72.5% vs 68.2%, p = 0.29), but REIs were twice as likely to support lower limit BMI restrictions compared to MFMs (56.2% vs 28.4%, p < 0.0001). Those who supported upper BMI restrictions were more likely to be female and report existing institutional BMI cutoffs. The majority of respondents (99.3%) believed that an official statement to guide clinicians should be issued by a national professional organization., Conclusions: Although practice patterns widely vary, the majority of REIs and MFMs believe that there should be a BMI cutoff above which women should not be offered immediate fertility treatment. Furthermore, there is a reported need for a written statement by a national professional organization to guide clinical practice and to ensure that OB/GYN subspecialists are providing consistent, fair, and safe recommendations to infertile women at the extremes of BMI.

Context: Infertility affects 10% of the reproductive-age population. Even the most successful treatments such as assisted reproductive technologies still result in failed implantation. In addition, adverse pregnancy outcomes associated with infertility have been attributed to these fertility treatments owing to the presumed epigenetic modifications of in vitro fertilization and in vitro embryo development. However, the diagnosis of infertility has been associated with adverse outcomes, and the etiologies leading to infertility have been associated with adverse pregnancy and long-term outcomes., Evidence Acquisition: We have comprehensively summarized the data available through observational, experimental, cohort, and randomized studies to better define the effect of the underlying infertility diagnosis vs the epigenetics of infertility treatments on treatment success and overall outcomes., Evidence Synthesis: Most female infertility results from polycystic ovary syndrome, endometriosis, and unexplained infertility, with some cases resulting from a polycystic ovary syndrome phenotype or underlying endometriosis. In addition to failed implantation, defective implantation can lead to problems with placentation that leads to adverse pregnancy outcomes, affecting both mother and fetus., Conclusion: Current research, although limited, has suggested that genetics and epigenetics of infertility diagnosis affects disease and overall outcomes. In addition, other fertility treatments, which also lead to adverse outcomes, are aiding in the identification of factors, including the supraphysiologic hormonal environment, that might affect the overall success and healthy outcomes for mother and child. Further studies, including genome-wide association studies, epigenomics studies, and experimental studies, are needed to better identify the factors leading to these outcomes., (Copyright © 2019 Endocrine Society.)

Purpose: Meningiomas are more common in females and 70-80% express the progesterone receptor, raising the possibility that high-dose exogenous estrogen/progesterone exposure, such as occurs during fertility treatments, may increase the risk of developing a meningioma. The goal of this study was to report the incidence of prior fertility treatment in a consecutive series of female meningioma patients., Methods: A retrospective review (2015-2018) was performed of female patients with meningioma, and those with prior fertility treatment were compared to those without fertility treatment using standard statistical methods., Results: Of 206 female patients with meningioma, 26 (12.6%) had a history of fertility treatments. Patients underwent various forms of assisted reproductive technology including: in vitro fertilization (50.0%), clomiphene with or without intrauterine insemination (34.6%), and unspecified (19.2%). Median follow up was 1.8 years. Tumors were WHO grade I (78.6%) or grade II (21.4%). Patients who underwent fertility treatments presented at significantly younger mean age compared to those who had not (51.8 vs. 57.3 years, p = 0.0135, 2-tailed T-test), and on multivariate analysis were more likely to have multiple meningiomas (OR 4.97, 95% CI 1.4-18.1, p = 0.0154) and convexity/falx meningiomas (OR 4.45, 95% CI 1.7-11.5, p = 0.0021)., Conclusions: Patients in this cohort with a history of fertility treatment were more likely to present at a younger age and have multiple and convexity/falx meningiomas, emphasizing the importance of taking estrogen/progesterone exposure history when evaluating patients with meningioma. Future clinical studies at other centers in larger populations and laboratory investigations are needed to determine the role of fertility treatment in meningioma development.

In both women and men, chronic kidney disease (CKD) is associated with decreased fertility. Though a multitude of factors contribute to the reduction in fertility in this population, progressively impaired function of the hypothalamic-pituitary-gonadal axis appears to play a key role in the pathophysiology. There is limited research on strategies to manage infertility in the CKD population, but intensive hemodialysis, kidney transplantation, medication management and assisted reproductive technologies (ART) have all been proposed. Though fertility and reproductive care are reported as important elements of care by CKD patients themselves, few nephrology clinicians routinely address fertility and reproductive care in clinical interactions. Globally, the average age of parenthood is increasing, with concurrent growth and expansion in the use of ART. Coupled with an increasing prevalence of CKD in women and men of reproductive age, the importance of understanding fertility and reproductive technologies in this population is highlighted. This review endeavors to explore the female and male factors that affect fertility in the CKD population, as well as the evidence supporting strategies for reproductive care.

Aim: To determine the efficacious treatment for infertile couples, we assessed the impact of infertility factors including endometriosis on assisted reproductive technology (ART) and non-ART treatment, and the effect of age in infertility treatment outcomes was also investigated., Methods: The medical records of 1864 females, infertile patients from January 2000 to December 2015 at our hospital, were retrospectively reviewed under the approval of the Institutional Review Board. We extracted 10 representative factors and calculated the cumulative live birth rate (CLBR) in these patients. Multivariate analysis of ART and non-ART treatment was performed to assess the impact of infertility factors, and the age-related decline in cumulative live birth rate was calculated by creating eight age-stratified subgroups., Results: In total, 21.9% and 49.4% of the patients conceived after being treated with non-ART and ART, respectively. Multivariate analysis revealed that age > 35, advanced endometriosis defined by the revised American Society for Reproductive Medicine classification system stages III to IV, and the past history or current presence of uterine fibroid had significantly negative impact on the outcome of non-ART. Age stratification revealed that advanced endometriosis adversely affected the outcome of non-ART, especially for patients in their 30s. Assisted reproductive technology treatment for patients with advanced endometriosis was shown to be efficacious because the negative impact had been diminished., Conclusion: Considering that non-ART treatment had limited role in patients with advanced endometriosis, prompt initiation of ART in these patients aged as young as 30 years can be recommended to achieve conception., (© 2018 Japan Society of Obstetrics and Gynecology.)

Objective: Infertile women requiring ovarian stimulation and assisted reproduction techniques (ART) are faced with difficult issues. The fear that using hormones could increase their risk of cancer is the most significant. One of the main challenges for assessing cancer risk after ART is the difficulty to separate it from the underlying condition of infertility per se. The delay or the inability to achieve a pregnancy is an important risk factor for breast, endometrial and ovarian cancer. We analyzed the current literature on the topic., Materials and Methods: The published literature in Medline and Cochrane was screened using the following keywords: ovulation induction, reproductive techniques, clomiphene, in vitro fertilization, fertility agents, female/adverse effects, female/toxicity gonadotropins/ adverse effects or gonadotropins/toxicity and "neoplasms or cancer"., Results: A total of 95 articles were evaluated. Limited evidence suggests that high doses or many cycles of clomiphene citrate could increase the risk of endometrial cancer, although the confounding factors of polycystic ovarian disease and overweight are not always considered. In some studies, ART modestly increased the risk of borderline ovarian cancer. Fertility treatments do not increase the risk of breast, cervical, endometrial and ovarian cancers, thyroid, melanoma and colon cancer., Conclusions: Women can be reassured that fertility drugs do not appear to significantly increase the risk of invasive ovarian, endometrial, breast or other cancers, while achieving a pregnancy at an earlier age is a significant protective factor.

Encounters for infertility care are opportunities to assess and update immunization status. Women of reproductive age are often unaware of their need for immunization, their own immunization status, and the potentially serious consequences of preventable disease on pregnancy outcome. The purpose of this ASRM Practice Committee document is to summarize current recommendations regarding vaccinations for women of reproductive age. This document replaces the ASRM Practice Committee document titled, "Vaccination guidelines for female infertility patients," last published in 2013 (Fertil Steril 2013;99:337-9)., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A growing number of infertile women undergo assisted reproductive technology (ART). Older maternal age and the presence of comorbidities may affect cardiovascular (CV) women health. Safety aspects are central in risk assessment; we report the experience of internal medicine clinical setting at the ART center., Materials and Methods: we investigated 243 infertile women (110 autologous and 133 oocyte donation [OD]); cardiometabolic parameters and CV risk factors were investigated during the clinical evaluation., Results: We observed high prevalence of dyslipidemia (62.9%), smoking habit (27.5%), and body mass index (26.7%). Waist ≥80 cm was present in 65%, and waist to hip ratio (WHR) value >0.80 in 60.5% of women. The prevalence of migraine with aura, hypertension, and diabetes was 5.3%, 4.9%, and 4.5%, respectively. By evaluating variables according to autologous or OD ART, we observed that OD women were older than autologous, p < 0.0001. Overweight and obesity prevalence was higher in OD group; waist and WHR were significantly higher in autologous than in OD group (75% vs. 57%, p = 0.005, and 91.8% vs. 34.6%, p = 0.01, respectively). We observed a statistically significant unfavorable risk profile in OD in comparison to autologous women (p = 0.003); in particular, 60% of OD women carried 3-5 CV risk factors, and 8.3% carried at least six CV risk factors., Conclusions: The experience of an internal medicine clinic at the ART center strongly underlies the relevance of a careful medical evaluation before attempting ART, and suggests the opportuneness of a structured internal medicine clinic in every gynecology setting to better frame risk profile.

Objective: To examine the risk for cyanotic congenital heart diseases (CCHDs) among live births in the USA, resulting from various forms of infertility treatments., Methods: This study is a cross-sectional analysis of live births in the USA from 2011 to 2014. Infertility treatments are categorised into two of the following groups on birth certificates: assisted reproductive technology (ART) fertility treatment (surgical egg removal; eg, in vitro fertilisation and gamete intrafallopian transfer) and non-ART fertility treatment (eg, medical treatment and intrauterine insemination). We compared the risk for CCHD in ART and non-ART fertility treatment groups with those infants whose mothers received no documented fertility treatment and were naturally conceived (NC)., Results: Among 14 242 267 live births from 2011 to 2014, a total of 101 494 live births were in the ART and 81 242 resulted from non-ART fertility treatments. CCHD prevalence in ART, non-ART and NC groups were 393/100 892 (0.39%), 210/80 884 (0.26%) and 10 749/14 020 749 (0.08%), respectively. As compared with naturally conceiving infants, risk for CCHD was significantly higher among infants born in ART (adjusted relative risk (aRR) 2.4, 95% CI 2.1 to 2.7) and non-ART fertility treatment groups (aRR 1.9, 95% CI 1.6 to 2.2). Absolute risk increase in CCHD due to ART and non-ART treatments were 0.03% and 0.02%, respectively. A similar pattern was observed when the analysis was restricted to twins, newborns with birth weights under 1500 g and gestational age of less than 32 weeks., Conclusions: Our findings suggest an increased risk for CCHD in infants conceived after all types of infertility treatment., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Genital and sexual pain is still neglected. Consequences may be dramatic, since infertility and sexual dysfunction may be reciprocally linked. This is the first study to focus on the identification of cases of vaginismus in the ART scenario and on the introduction of intra-cycle interventions as part of a comprehensive, integrated and patient-centered perspective., Methods: This observational prospective study looked into 425 IVF/ICSI cycles and 226 frozen embryo transfers carried out from January 1, 2015 to December 31, 2016, and found seven cases of vaginismus. Within a six-month period, a questionnaire placed on SurveyMonkey was sent twice to 228 ART centers in Latin America. The purpose was to learn how often cases of vaginismus were found in ART centers and the perceptions around the presence of this condition., Results: The few centers that took the time to answer the questionnaire (24/10.5%) stated that the number of cases in which they had trouble performing control ultrasound examination or needed to perform transfers with patients under sedation was not significant. Although 81% agreed that the incidence of these conditions is low, no references were made to cases of vaginismus, dyspareunia or sexual dysfunction. Our multidisciplinary team found seven cases of vaginismus, involving women with higher education degrees with a mean age of 37.8 years and married for a mean of four years. Although two reported they were able to tolerate intercourse, all reported undergoing treatments such as using vaginal dilators (3), psychotherapy (4) and psychiatric care (1). The care provided by the staff was designed to mitigate patient suffering., Conclusion: Gentle care and sensitive listening should be integral components in the work of multidisciplinary teams to identify women with vaginismus and offer couples better quality treatment.

Background and Objective: Infertility is a common disease that in about one third of cases has a female cause and often requires assisted reproduction technologies (ART) to conceive. Also thyroid autoimmunity (TAI), with or without hypothyroidism, is a common disease, particularly in females, and referral for endocrine consultation is not infrequent., Discussion: In the last 15 years a remarkable amount of studies has been published that investigated the pathophysiology of women suffering from TAI, who undergo ART. Due to insufficient sample size, data about the association between infertility and TAI/subclinical hypothyroidism are conflicting. In relation to pregnancy rate, miscarriage, and live births (primary outcomes) data of the literature do not allow to clearly demonstrating an unfavorable impact attributable to TAI/subclinical hypothyroidism; however, secondary outcomes like ovarian reserve or oocytes quality look like worsened., Conclusion: For sure, the therapeutic regimens used for controlled ovarian hyperstimulation (COH) induce a deterioration of thyroid function in patients suffering from TAI [with or without Levothyroxine (LT4) treatment]. This picture places patients in a condition of increased risk of developing untimely TSH elevation during fertilization; then, it is reasonable that a patient, above all if thyroid antibody positive, would have a TSH value <2.5mIU/L before undergoing COH, and that would be strictly monitored to start or increase LT4 treatment, when necessary., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Infertility is a condition in which a woman has not been pregnant despite having had normal intercourse for 1 year. The number of unexplained infertile females is increasing because of late marriage customs, as well as environmental and lifestyle habits. In Korea, infertile females have been treated with Korean medicine (KM). However, these effects have not been objectively confirmed through clinical trials. Therefore, this study was conducted to demonstrate the effectiveness of herbal medicine treatment in infertile patients and to demonstrate the economic feasibility through economical evaluation with assisted reproductive technology.This study is designed as a multicenter, single-arm clinical trial. All participants included will be from 3 Korean Medicine hospitals in Korea and will voluntarily sign an informed consent agreement. All recruited patients will conduct related surveys and tests, and be provided with treatment according to their menstrual cycle. Patients will take herbal medicines for 4 menstruation cycles and receive acupuncture and moxibustion treatment at 3 times (menstrual cycle day 3, 8, 14) during 4 menstruation cycles. They will also undergo an approximately 4 menstrual cycle treatment period, and 3 menstrual cycle observation period. If pregnant during the study, participants will take the herbal medicine for implantation for about 15 days. In this study, the primary outcome will be the clinical pregnancy rate, whereas the secondary outcome will include the implantation rate, ongoing pregnancy rate, and live birth rate.Ultimately, this study will provide clinical data regarding the effectiveness and safety of KM treatment for females with unexplained infertility and important evidence for establishing standard KM treatments for unexplained infertility. Moreover, we will identify the most cost-effective way to treat unexplained infertility., Trial Registration Identifier: Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002235. Date: February 21, 2017 (retrospectively registered)., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The socio-demographic and clinical characteristics of 246 consecutive couples seeking assisted conception in a university teaching hospital in Nigeria from inception in 2011 till 2014 were reviewed restrospectively. Eighty-five (34.5%) were in the 35-40 years age group. The body mass index of the women showed that 111 (45.1%) were overweight. One hundred and ninety five (88%) were referred on account of secondary infertility. The mean duration of infertility was 9.6 ± 4.8 years. Major factors identified were male factor 128 (52%), ovarian/age-related decline in fertility 107 (43.5%), tubal 83 (33.7%) and combined male/female factor 71 (28.9%). One hundred and ninety (77.2%) clients seeking assisted conception were Christians at advanced age (greater than 35 years) with a longstanding duration of infertility of more than 10 years. Government, private and religious organisations need to raise public awareness about the availability of in-vitro fertilisation services as well as encourage early resort to assisted reproductive technologies. Impact statement What we already know: Secondary infertility due mainly to tubal factor is reported to be the commonest cause of infertility in developing countries like Nigeria and clients affected seek assisted reproductive techniques late. What the results of this study add: Male factor infertility is more common amongst infertile couples seeking in vitro fertilisation in LASUTH. The implications of the findings for practice and/or further research: A thorough examination of the male partner followed by investigation is vital at the initial visit so that they can be referred early for assisted conception.

Study Question: How common were children among infertile couples?, Summary Answer: A total of 61.7% of infertile couples presenting for care subsequently had live born children 13.1 years after first being clinically assessed, with a mean of 1.7 children among those who had at least one., What Is Known Already: While the prognoses for infertile couples undertaking specific treatments have been well described, less is known about those not undergoing these treatments or the total number of children. This information is necessary for decision-making in many individual cases; not knowing this has been cited by patients and clinicians as impeding implementation of care., Study Design, Size, Duration: The sole provider of specialist fertility care for the two southern-most regions in New Zealand enroled 1386 infertile couples from 1998 to 2005 in a longitudinal study with follow-up on all births until the end of 2014. Couples were followed in care for a median of 1.1 years and median follow-up for births was 13.1 years., Participants/materials, Setting, Methods: Clinic-collected data were linked to national maternity data to extend follow-up past the end of clinical contact. The primary outcome was the total number of live born children. Hurdle regression was used to investigate factors associated with resolving infertility and the total number of children., Main Results and the Role of Chance: Infertility was resolved with a live birth by 61.7% (95% CI 59.1-64.2%) of couples; just over half of all first births were treatment-dependent. Among couples who resolved their infertility, 55.6% (52.2-58.9%) had at least one additional child and the mean number of children was 1.7. While female age strongly influenced outcomes, one-third of women aged 40-41 years had a child, not significantly less than those in their late 30s. The lowest levels of resolution occurred in women aged ≥42 years, couples who were infertile for >4 years and women with a BMI ≥ 35 kg/m2. Moderate obesity did not affect outcomes., Limitations, Reasons for Caution: The main limitation of this study was insufficient data to investigate male factor infertility outcomes. It is also possible that treatment-dependent resolution could be higher in more recent cohorts with the increased use of ART., Wider Implications of the Findings: Outcomes in these couples are comparable to those seen in other studies in high-income countries despite the relatively low contribution of ART. The prognosis for most infertile couples is positive and suggests many will not require treatment. Further research is needed to inform best practice for women in their early forties or with moderate obesity, and to develop prediction models that are more relevant for the initial management of infertility., Study Funding/competing Interest(s): This study was co-funded by a University of Otago PhD Scholarship and the Department of Women's and Children's Health, University of Otago. There were no competing interests to declare., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Objective: To compare the impact of first-line assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI]-IVF) and first-line colorectal surgery followed by ART on fertility outcomes in women with colorectal endometriosis-associated infertility., Design: Retrospective matched cohort study using propensity score (PS) matching (PSM) analysis., Setting: University referral centers., Patient(s): A total of 110 women were analyzed from January 2005 to June 2014. A PSM was generated using a logistic regression model based on the age, antimüllerian hormone (AMH) serum level, and presence of adenomyosis to compare the treatment strategy., Intervention(s): First-line surgery group followed by ART versus exclusive ART with in situ colorectal endometriosis., Main Outcome Measure(s): After PSM, pregnancy rates (PRs), live-birth rates (LBRs), and cumulative rates (CRs) were estimated., Result(s): After PSM, in the whole population, the total LBR and PR were 35.4% (39/110) and 49% (54/110), respectively. The specific cumulative LBR at the first ICSI-IVF cycle in the first-line surgery group compared with the first-line ART was, respectively, 32.7% versus 13.0%; at the second cycle, 58.9% versus 24.8%; and at the third cycle, 70.6% versus 54.9%. The cumulative LBRs were significantly higher for women who underwent first-line surgery followed by ART compared with first-line ART in the subset of women with good prognosis (age ≤ 35 years and AMH ≥ 2 ng/mL and no adenomyosis) and women with AMH serum level < 2 ng/mL., Conclusion(s): First-line surgery may be a good option for women with colorectal endometriosis-associated infertility., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the impact of bariatric surgery on obese infertile women seeking an assisted reproductive technology., Methods: All obese women with a history of assisted reproductive technology (ART) failure that underwent ART treatment cycles both prior to and following bariatric surgery were included. ART outcomes were compared evaluating the duration and dose of gonadotrophins used; the measurement of day 3 FSH; the anti-mullerian hormone dosage; the number of follicles >15 mm; the number of retrieved and fertilized oocytes; the number of metaphase II, metaphase I and germinal vesicle oocytes; the number of embryos obtained; the number of top-quality oocytes and embryos; the number of transferred embryo; the pregnancy rate and the live birth rate., Results: Forty women were included. The total number of gonadotropin units required and in the length of stimulation following bariatric surgery decreased (p = .001), with an increase of the number of follicles ≥15 mm (p = .005), of retrieved oocytes (p = .004), of top-quality oocytes (p = .001) and metaphase II oocytes (p = .008). More oocytes were fertilized (4.2 ± 1.7 vs 5.3 ± 2.4; p = .02). After surgery, we have registered also a better number of top-quality embryos (0.5 ± 0.6 vs 1.1 ± 0.9; p = .003). Pregnancy rate following the bariatric surgery increased to 15/40 (37.5%) (p < .001), and live birth rate (LBR) increased to 14/40 (35%) in the post-surgery group (p<. 001)., Conclusions: Although additional research would be useful to draw definitive conclusion, our results appear to be encouraging enough to suggest the use of bariatric surgery in obese infertile women seeking an ART treatment.

Objective: To study whether infertility treatments, including IVF and non-IVF fertility treatments, are associated with diseases of placental insufficiency in early gestation. First trimester placental volumes by ultrasound and chorionic villi weight during sampling (CVS) were performed to detect differences between pregnancies conceived spontaneously versus with fertility treatments., Design: Retrospective cohort., Setting: Academic tertiary center., Patient(s): Women with singleton pregnancies undergoing CVS and first trimester ultrasound from April 2007 to November 2015., Intervention(s): Estimated placental volume (EPV) was calculated from ultrasound images using a validated computation and CVS estimated tissue weight was performed using a validated visual analogue scale., Main Outcome Measure(s): Adjusted linear regression was used to compare EPV and CVS weight based on mode of conception., Result(s): A total of 1,977 spontaneous and 334 conceived with fertility treatments (133 non-IVF and 201 IVF) pregnancies were included. Significant differences in maternal age, gravidity, hypertension, and smoking status were identified. EPV and CVS weight were correlated with maternal age, gestational age, and maternal hypertension. Adjusted linear regression showed no difference in EPV in pregnancies conceived with fertility treatments versus spontaneously. The CVS weight was significantly lower in the IVF conceptions in unadjusted univariate analyses. However, after adjusted regression, this was no longer significant., Conclusion(s): Mode of conception does not appear to affect first trimester placental size. As differences in maternal age, hypertension, and smoking status differ among the groups and are correlated to placental size, it may be the underlying patient population leading to abnormal placentation and insufficiency, not the fertility treatments used., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To describe the relationship between severe diminished ovarian reserve (DOR) and assisted reproductive technology outcomes., Study Design: Retrospective cohort including all United States’ fertility centers reporting to the CDC National ART Surveillance System, 2004–2012. Among women aged <41 (504,266 fresh autologous IVF cycles), we calculated cancellation rate/cycle and pregnancy rate/transfer, stratified by age, by maximum follicle-stimulating hormone (FSH). Cancellation rate per cycle and pregnancy, live birth, and miscarriage rates per transfer were compared among women with and without DOR. We used multivariable log binomial regression, stratified by age, to calculate adjusted relative risk (aRR) for the association between DOR and these outcomes and, within DOR groups, between stimulation type and outcomes., Results: Cancellation rate/cycle increased with increasing FSH and with DOR severity. For women aged <35 who underwent transfer, aRR for pregnancy and live birth indicated slightly reduced likelihood of these outcomes (severe vs. no DOR); confidence intervals approached the null. Among women with severe DOR, stimulation type was not associated with likelihood of pregnancy or live birth per transfer in any group except women ages 38–40., Conclusion: Women with severe DOR are at significantly increased risk of cancellation; however, those who undergo transfer have pregnancy and live birth chances similar to those of women without DOR after controlling for cycle characteristics.

Objective: To study the association between endometriosis and risk of pre-eclampsia, cesarean section, postpartum hemorrhage, preterm birth, and small for gestational age (SGA), in a large Danish birth cohort, while taking fertility treatment into account., Design: Population-based study., Setting: Not applicable., Patient(s): A total population of 82,793 singleton pregnancies from the Aarhus Birth Cohort (1989 through 2013); 1,213 women had a diagnosis of endometriosis, affecting 1,719 pregnancies., Intervention(s): None., Main Outcome Measure(s): Pre-eclampsia, cesarean section, postpartum hemorrhage, preterm birth, and SGA., Result(s): Endometriosis was associated with an increased risk of preterm birth (adjusted odds ratio [AOR] 1.67, 95% confidence interval [CI] 1.37-2.05), with the risk being highest for very preterm birth (AOR 1.91, 95% CI 1.16-3.15). Compared with unaffected women, women with endometriosis also had an increased risk of pre-eclampsia (AOR 1.37, 95% CI 1.06-1.77) and cesarean section (AOR 1.83, 95% CI 1.60-2.09). Assisted reproductive technology did not explain these findings. No association was found between endometriosis and postpartum hemorrhage or SGA., Conclusion(s): Women with endometriosis were at increased risk of pre-eclampsia, preterm birth, and cesarean section, irrespective of use of assisted reproductive technology., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Until recently, adenomyosis has been associated with multiparity, not impaired fertility. Currently, adenomyosis is diagnosed with increasing frequency in infertile patients since women delay their first pregnancy until their late 30s or early 40s. Although an association between adenomyosis and infertility has not been fully established, based on the available information, recent studies suggested that adenomyosis has a negative impact on female fertility. Several uncontrolled studies with limited data also suggested that treatment of adenomyosis may improve fertility. This article discusses (i) the hypothesis and epidemiology of adenomyosis, (ii) diagnostic techniques, (iii) clinical evidence of correlation between adenomyosis and infertility, (iv) proposed mechanism of infertility in women with adenomyosis, (v) different treatment strategies and reproductive outcomes, and (vi) assisted reproductive technology outcome in women with adenomyosis.

Objective: To determine whether women with a history of fertility problems have a higher risk of gestational diabetes mellitus (GDM) than women without a history of fertility problems after adjustment for maternal factors., Design: Nationwide population-based cohort study., Setting: Not applicable., Patient(s): All live and stillbirths during 2004-2010 among women with fertility problems (n = 49,616) and women without fertility problems (n = 323,061) were identified by linkage between the Danish Medical Birth Registry and the Danish Infertility Cohort. Information on GDM was obtained from the Danish National Patient Registry., Intervention(s): None., Main Outcome Measure(s): Odds ratios and 95% confidence intervals for the association between fertility problems and risk of GDM after adjustment for potentially confounding factors, including maternal age, prepregnancy BMI, parity, parental history of diabetes, level of education, and smoking during pregnancy., Result(s): In total, 7,433 (2%) pregnant women received a diagnosis of GDM. Multivariate analysis showed that pregnant women with a history of fertility problems had a statistically significantly higher risk of GDM than pregnant women without fertility problems. In stratified analyses, the association between fertility problems and risk of GDM attenuated with increasing age and was more pronounced among primiparous women and women with polycystic ovary syndrome., Conclusion(s): Our findings suggest that pregnant women with a history of fertility problems are at increased risk of GDM., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To explore factors affecting the incidence of ectopic pregnancy (EP) in assisted reproductive technology (ART)., Design: A retrospective cohort study on the incidence of EPs in IVF/intracytoplasmic sperm injection (ICSI) and IUI cycles from June 2009 to August 2015. Age of patients, tubal factor infertility, type of cycle (fresh or thawed), embryo being transferred (cleavage embryo or blastocyst), and number of embryos transferred were analyzed to explore their relationship with the incidence of EP., Setting: Teaching hospital., Patient(s): A total of 18,432 pregnancies resulting from ART treatment were retrospectively analyzed., Intervention(s): None., Main Outcome Measure(s): Ectopic pregnancy rate., Result(s): For IVF/ICSI cycles, the incidence of EP was different between cycles transferred with cleavage embryo and blastocyst (3.45% vs. 2.47%). In multivariate logistic regression analysis, tubal infertility was associated with EP (adjusted odds ratio 1.716, 95% confidence interval 1.444-2.039). For IUI cycles, EP was significantly higher in stimulated cycles compared with natural cycles (2.62% vs. 0.99%). The EP rate in cycles with sperm from donor and husband was 1.08% and 3.54%, respectively. However, when patients were stratified according to tubal infertility, the EP rate increased with level of peak estrogen. In thawed embryo transfer cycles, the EP rate was lower in blastocyst transfer cycles and in cycles transferred with fewer embryos., Conclusion(s): Irrespective of tubal infertility, for fresh IVF/ICSI cycles the rate of EP is positively associated with ovarian stimulation; for thawed IVF/ICSI cycles, blastocyst transfer or transfer with fewer embryos reduces the EP rate. In IUI cycles, EP is associated with sperm source., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Clomiphene and assisted reproductive technologies (ART) are methods used to help subfertile couples become pregnant. ART has been reported to be associated with neural tube defects (NTDs) in offspring. To evaluate these associations, we studied mothers of 219 cases and 4,262 controls from the Slone Epidemiology Center Birth Defects Study (1993-2012) who were interviewed within 6 months after delivery about pregnancy events, including use of fertility treatments. We considered exposures to clomiphene (without ART) and ART during the periconceptional period. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals, controlling for education and study center. We observed elevated adjusted odds ratios of 2.1 (95% confidence interval: 0.9, 4.8) and 2.0 (95% confidence interval: 1.1, 3.6) for clomiphene and ART exposure, respectively. We performed a mediation analysis to assess whether the observed elevated NTD risk was mediated through multiple births. For clomiphene exposure without ART use, the direct effect estimate of the adjusted odds ratio (aORDE) was 1.7 and the indirect effect estimate (aORIE) was 1.4. Conversely, for ART exposure, the aORDE was 0.9 and the aORIE was 2.5. Our findings suggest that relatively little of the clomiphene-NTD association is mediated through the pathway of multiple births, while the ART-NTD association was explained by the multiple-births pathway., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

One of the barriers to access to fertility care is the relative complexity of fertility treatments. If these can be simplified, more patients may be able to take advantage of these treatments. In this overview, we review the potential benefits of simplifying ovarian stimulation by the means of four distinct methods: 1) using mild stimulation for IVF cycles; 2) using in vitro maturation to allow for the retrieval of oocytes that are not yet fully mature yet have the potential to result in live births; 3) conducting IVF in modified natural cycles which use no exogenous FSH stimulation; and 4) allowing embryo culture to take place in a novel intravaginal incubation system. These methods are considered to be somewhat unconventional, yet they have all been shown to lead to live births. In the era of individualized patient care, these techniques present viable alternatives to standard treatment. As experience and outcome data accumulate, they may prove to be not just alternatives to standard treatment, but potentially first-line treatment choices., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Health care professionals make the medical care of infertility patients a priority, with the goal of achieving a singleton pregnancy for each. Patients who never seek out care, who do not return for treatment after the diagnostic workup, or who drop out of treatment are rarely noticed. Yet this is the outcome for the majority of patients, and the primary reason after financial for treatment termination is the emotional aspect. Attending to the psychological needs of our patients must become a higher priority, to provide all patients true access to care., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To study the social dimension of age-related female infertility through an analysis of three key themes: the personal life histories of infertile women over 40 years of age; representations of age and the desire to become pregnant after age 40; opinions of French legislations framing Assisted Reproductive Technologies, age limits, egg donation, and egg freezing for non-medical reasons., Methods: This qualitative sociological study was based on semi-structured interviews with infertile women over age 40 going through fertility treatments. The interviews contained three parts: personal and relationship histories; experiences related to age; opinions related to French legislation., Results: Twenty-three interviews were conducted; each lasting between 90 to 120minutes. Far from having similar life histories, the women interviewed had very different backgrounds leading to their desire for a pregnancy after 40 years of age. From the beginning of their fertility treatments, they perceived a "race against the clock". This feeling of urgency accompanied their experiences and was related to the desire to not be too old for their future child. The women interviewed were mainly in favor of loosening French bioethical laws in order to avoid the need to travel abroad to pursue fertility treatments., Conclusion: The profiles studied attest to a growing gap between biological and biographical temporalities, as well as an inability of women to reduce their desire for a child. Faced with this disparity, egg donation and egg freezing were seen as practical solutions., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)