Search

Background: Infertility is a reproductive health problem which affects not only individuals, families and social populations. Recently, the infertility rate in China has a trend of increase year by year, and few studies have reported the infertility rate in Henan Province, China. The aim of this study was to investigate the current prevalence and associated factors of infertility among women of childbearing age in Henan Province, China., Methods: This cross-sectional study was conducted from March 2019 to October 2019. We sampled 765 women who were 20-49 years old in eight hospitals of four cities in Henan Province, China. This survey included a questionnaire, physical examination, vaginal ultrasound examinations, and serum anti-Mullerian hormone (AMH) assessment, all of which were conducted under uniform standards by trained personnel. According to the data collected from questionnaire, participants were divided into infertile and fertile groups and analyzed associated factors., Results: Among all the 765 participants in this study, the prevalence of infertility was 24.58%. The prevalence of primary infertility was 6.54%, and the prevalence of secondary infertility was 18.04%. In logistic multivariate regression analyses, infertility was associated with age (p < 0.001), history of gynecological surgery (p < 0.001), sweet food (p = 0.003) and decreased ovarian reserve (DOR) (p < 0.001). After further analyses, factors associated with primary infertility were age of marriage (p = 0.006), age of first sexual intercourse (p = 0.003), long-term air-conditioning environment (p < 0.001), decreased ovarian reserve (p = 0.005) and age (p = 0.002). And factors associated with secondary infertility were history of gynecological surgery (p < 0.001), decreased ovarian reserve (p = 0.002), waist-to-hip ratio (WHR) above 0.85 (p = 0.043), delivery times (p = 0.001) and ages (p < 0.001)., Conclusion: The prevalence of infertility among women aged 20-49 was 24.58% and only 61.17% infertile women sought medical help in Henan Province, China. Age, history of gynecological surgeries and DOR may increase the risk of infertility. Local public health departments and medical professionals need to discharge their duty of reducing the high incidence of infertility and protecting women's reproductive health., (© 2021. The Author(s).)

Objectives: To determine the risk of having OSA in a cohort of female subjects who are infertile and the odds of being infertile in women with OSA., Patients and Methods: A nationwide, case-control study of female patients 20 years or older diagnosed with female infertility living in Taiwan, from January 1, 2000, through December 31, 2013 (N = 4,078). We identified women who were infertile and created a 2:1 matched control group with women who were not infertile. We used multivariable logistic regression analysis to further estimate the effects of OSA on female infertility., Results: In this 14- year retrospective study, we included 4,078 patients having an initial diagnosis of female infertility. Of those women with infertility, 1.38% had a history of OSA compared with 0.63% of fertile controls (p = 0.002). The mean ages in the study groups were 32.19 ± 6.20 years, whereas the mean ages in the control groups were 32.24 ± 6.37years. Women with OSA had 2.101- times the risk of female infertility compared to women without OSA (p<0.001)., Conclusion: Our study showed that OSA is more commonly seen in infertile women and increases the odds that a woman will be infertile. More studies need to be done on the whether or not diagnosing and treating OSA can decrease the rate of infertility., Competing Interests: The authors have declared that no competing interests exist.

Background: Infertility processis a strestfull period that effects of couple's life, especially their working life. It can be difficult for women with fertility problems to fulfill work responsibilities during infertility treatment. The current study aimed to explore effects of infertility treatment on women's stress and hence working life. There is limited literature related to effect of this treatment on women working life so this is important issue worldwide., Subjects and Methods: This was a cross-sectional descriptive study and 200 women undergoing infertility treatment participated. Our participants were primary infertile working women who had received at least one-cycle of infertility treatment before being invited to be part of study. An Introductory Data and Fertility History Form, Infertility Treatment and Working Performance Questionnaire and Visual Analogue Stress Scale were administered over-3 month period., Results: More than half of women (53%) reported that they experienced problems related to ask the manager for the leave because of some procedure during the infertility treatment. Fear of administrator, not being able to focuse on work, not being understood by collegues, a negative impact on career, increase in work stress were problems reported by women. Also participants reported adversity in sharing infertility treatment with male administrators., Conclusions: The study found that infertility treatment process affect women's working life negatively. Therefore health professionales should improve employers awareness about impact of infertility treatment on working life for purposs of improving professional support needed during this treatment time. Women should be encouraged to share feelings/problems they experience with employers/colleagues.

Introduction: Transvaginal ultrasound is fundamental for the mapping of endometriosis, and the imaging criteria have been clearly described for different organs study. However, no specific ultrasonographic signs of tubal endometriosis have been reported, with the exception of hydrosalpinx, which is the expression of an extreme tubal damage and obstruction. The detection of tubal pathology in infertile patients is fundamental, therefore the aim of the study was to evaluate incidence of tubal endometriosis in infertile patients, and to analyze ultrasonographic signs useful for detection of this condition., Material and Methods: It is a single-center, retrospective cohort study. All 500 consecutive infertile women who underwent laparoscopic surgery for endometriosis were included. The preoperative workup included transvaginal ultrasound and was compared to intraoperative findings and histologic study., Results: The incidence of tubal endometriosis in our study was 8%. Using hydrosalpinx as the ultrasonographic marker for tubal involvement the overall pooled, sensitivity and specificity of TVU were 12% (95%CI, 5-23%) and 99% (95%CI, 98-100%), respectively. If at least one ultrasonographic parameter like hydrosalpinx, periadnexal adhesions or ovarian cyst was considered as a sign of tubal endometriosis, a sensitivity, VPN and specificity were 94% (95% IC, 85-98%), 97% (95%IC, 93-99%) and 31% (95%CI, 27-36%), respectively., Discussion: Hydrosalpinx as ultrasonographic sign alone is characterized by a high specificity but low sensitivity for detection of tubal endometriosis; its sensitivity can be improved by the addition of other markers such as endometrioma and/or periadnexal adhesions., Competing Interests: Declaration of Competing Interest The authors declare that they wave no conflicts of interest and nothing to disclose., (Copyright © 2021. Published by Elsevier Masson SAS.)

Endometriosis is a chronic inflammatory disease that has been reported to be associated with immune system dysfunction. On the other hand, the effect of Vitamin D as an immune modulator and its relation with several autoimmune and inflammatory diseases has been previously investigated. Moreover, several studies have reported the polymorphisms of VDR and VDBP genes can change the functions of these molecules. Therefore, these polymorphisms may be influential on endometriosis pathogenesis. In this study, we aimed at evaluating the association between VDR gene (FokI (F/f), BsmI (B/b), ApaI (A/a), TaqI (T/t)), and VDBP gene (GC*1S, GC*1F, and GC*2) polymorphisms with endometriosis in Iranian women population. This case-control study was performed on 120 women with endometriosis and 110 healthy women. ARMS-PCR and PCR-RFLP methods were used to inspect polymorphisms in VDR and VDBP genes, respectively. Based on the results, there was no statistically significant difference between the cases with endometriosis and control subjects in terms of genotypes and allele frequencies of VDR and VDBP gene polymorphisms. These data suggest that VDR and VDBP gene polymorphisms may have no role in endometriosis susceptibility in Iranian women., (© 2021. Society for Reproductive Investigation.)

Introduction: clinical infertility is failure to conceive within a year of regular sexual intercourse by a non contracepting couple. Infertility care is costly and result in investigations being incomplete and inconclusive. It is therefore important to streamline investigations offered to infertile couples such that only the most cost effective tests are done. This paper explores the adequacy of investigations and treatments offered to women presenting for infertility care., Methods: the data used in this analysis was obtained from a cross sectional sample of 216 women who presented with infertility in public and private gynaecological clinics in Harare, Zimbabwe. Information on investigations and treatment offered to women presenting for care was extracted from hospital cards, case notes, laboratory and radiological reports. Data was analysed using STATA SE/15., Results: of the 178 (82.4%) who had ultrasound scan evaluation (USS) 50 (28.1%) had fibroids and 22 (12.4%) had polycystic ovaries. Tubal patency tests were done in 118 participants using (hystero-salpingogram) HSG alone in 62.7%, laparoscope and dye alone in 21.2% and both in 16.1% of them. Of the 97 (44.9%) men who had semen analysis 61 (62.9%) had abnormal parameters., Conclusion: this study reveals that evaluation for tubal patency and USS to rule out reproductive organ pathology are not being offered to all women with a diagnosis of infertility. Likewise, male partner semen evaluation is not being done in all male partners. There is a high prevalence of abnormal semen parameters. Studies should be done to understand why some male partners are not forthcoming in providing semen for analysis. It is important for protocols to be produced by professional bodies which prescribe the minimum basic investigations in couples with infertility., Competing Interests: The authors declare no competing interests., (Copyright: Mugove Gerald Madziyire et al.)

Purpose: To develop an innovative machine learning (ML) model that predicts personalized risk of primary ovarian insufficiency (POI) after chemotherapy for reproductive-aged women. Currently, individualized prediction of a patient's risk of POI is challenging., Methods: Authors of published studies examining POI after gonadotoxic therapy were contacted, and six authors shared their de-identified data (N = 435). A composite outcome for POI was determined for each patient and validated by 3 authors. The primary dataset was partitioned into training and test sets; random forest binary classifiers were trained, and mean prediction scores were computed. Institutional data collected from a cross-sectional survey of cancer survivors (N = 117) was used as another independent validation set., Results: Our model predicted individualized risk of POI with an accuracy of 88% (area under the ROC 0.87, 95% CI: 0.77-0.96; p < 0.001). Mean prediction scores for patients who developed POI and who did not were 0.60 and 0.38 (t-test p < 0.001), respectively. Highly weighted variables included age, chemotherapy dose, prior treatment, smoking, and baseline diminished ovarian reserve., Conclusion: We developed an ML-based model to estimate personalized risk of POI after chemotherapy. Our web-based calculator will be a user-friendly decision aid for individualizing risk prediction in oncofertility consultations., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

There is currently a dispute over the choice of ovulation induction treatment for infertile women with polycystic ovary syndrome (PCOS). The objective of this study is to compare the therapeutic effect of pulsed rhythmic administration protocol (PRAP) with conventional letrozole + human menopausal gonadotropin (HMG) in patients with clomiphene-resistance polycystic ovary syndrome (PCOS). A retrospective analysis of 821 intrauterine insemination (IUI) cycles between January 2015 and January 2020 was performed. Of these, 483 cycles were treated with a pulsed rhythmic administration protocol (PRAP), and 338 cycles were treated with conventional letrozole + HMG protocol (LHP). The therapeutic effect of the two protocols has been compared. The pregnancy rate was 18.07% in the LHP and 27.07% in the PRAP. The ongoing pregnancy rate in LHP was 14.46% and in PRAP was 22.73%. The research suggests that PRAP is more effective than LHP and could be an adequate ovulation induction strategy for the IUI cycle of patients with clomiphene-resistance PCOS., (© 2021. The Author(s).)

In this commentary, we discuss the associations between adenomyosis, fertility, and obstetric outcomes. A recent meta-analysis on the impact of adenomyosis on reproductive outcomes found a 43% reduction in the odds ratio (OR) for clinical pregnancy and a threefold increase in the risk of miscarriage in women with adenomyosis compared with controls. Moreover, adenomyosis seems to be strongly associated with pre-eclampsia with an OR of almost 8. Also, the risk for small for gestational age was almost fourfold increased, whereas for preterm deliveries was threefold increased. The presence of deep infiltrating endometriosis and adenomyosis seems associated with particularly adverse obstetric outcomes, especially concerning natural conception. Some observations suggest that the probability of clinical pregnancy is considerably low in these cases, around 11.8%. Although several methodological drawbacks prevent definitive conclusions, all these elements should be considered in counseling women with adenomyosis seeking pregnancy, especially in cases of IVF., (© 2021. Society for Reproductive Investigation.)

The roles of genital mycoplasmas including Mycoplasma genitalium (M. genitalium), Mycoplasma hominis (M. hominis), Ureaplasma urealyticum (U. urealyticum), and Ureaplasma parvum (U. parvum) in reproductive diseases are equivocal. To investigate whether genital mycoplasmas are risk factors of female infertility and adverse pregnancy outcomes, we performed a systematic review and meta-analysis. Electronic databases were searched for related studies. A random-effects model or fixed-effects model was employed to generate forest plots. Pooled odd ratios (ORs) with 95% confidence intervals (CIs) were applied to measure the strength of associations. Meanwhile, heterogeneity was evaluated by H statistic and I 2 statistic, and publication bias was explored by funnel plots based on Egger's test and Begg's test. The search yielded 2054 relevant records, and 35 articles were ultimately included for meta-analysis. M. genitalium was a significant risk factor for female infertility (OR, 13.03 [95% CI, 3.46-48.98]) and preterm birth (PTB) (OR, 1.81 [95% CI, 1.17-2.80]), but not for spontaneous abortion (SA) (OR, 0.58 [95% CI, 0.25-1.35]). M. hominis can significantly increase the potential risk of female infertility (OR, 1.56 [95% CI, 1.02-2.38]), SA (OR, 9.14 [95% CI, 4.14-20.18]), stillbirth (OR, 3.98 [95% CI, 1.39-11.36]), and premature rupture of membranes (PROM) (OR, 1.79 [95% CI, 1.26-2.55]), but was not associated with PTB (OR, 1.29 [95% CI, 0.78-2.15]). U. urealyticum had no significant risk effect on female infertility (OR, 0.68 [95% CI, 0.42-1.11]). Coinfections of M. hominis and Ureaplasma were significantly associated with female infertility, SA, and stillbirth, but not with PROM. On the basis of current evidences, this meta-analysis supports that M. genitalium is a risk factor for female infertility and PTB; M. hominis is a potential risk factor for female infertility, SA, stillbirth, and PROM; U. urealyticum has no significant association with female infertility; and the relationship of U. parvum with female infertility and adverse pregnancy outcomes needs to be paid more attention to and remains to be further revealed., (© 2021. Society for Reproductive Investigation.)

Our aim was to determine prospectively whether increased body mass index (BMI) affects endometrial receptivity through displacement of the window of implantation (dWOI) using the endometrial receptivity analysis (ERA), and whether this effect is BMI-dependent. We recruited a population of 170 infertile women with a normal uterus and no clinical history of recurrent miscarriage or implantation failure. These women were divided into four groups according to BMI: normal weight (18.5-24.9 kg/m 2 ; n = 44), overweight (25-29.9 kg/m 2 ; n = 29), class I obese (30.0-34.9 kg/m 2 ; n = 54), and class II and III obese (> 35 kg/m 2 ; n = 43). We also assigned the patients to one of two larger BMI cohorts: non-obese (normal weight and overweight; n = 73) and obese (class I, II, and III obese; n = 97). We compared analytical and clinical data and dWOI in these categories, finding significant metabolic differences in glycemia, TSH, insulin, HDL cholesterol, LDL cholesterol, triglycerides, and systolic and diastolic blood pressure among the different BMI groups. One-day dWOI increased significantly with BMI, and significant differences were observed in the non-obese versus obese categories (9.7% vs 25.3 %, respectively (p = 0.02)). dWOI was most pronounced in patients with class II-III obesity. In addition, displacement was longer as BMI increased since ERA revealed a higher proportion of displacements of 1 day than of 12 h and showed they were predominantly pre-receptive. In conclusion, obesity has a negative effect on endometrial receptivity through delaying of the WOI, which increases in function of BMI as well as the metabolic disturbances of the patient., (© 2021. Society for Reproductive Investigation.)

Background: Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Plasmid gene protein 3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA)., Methods: We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI ≥ 50 000; low-positive was MFI > 551-<50 000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (CI) were compared for women with chlamydial infection, self-reported PID, and infertility., Results: Of 2339 women aged 18-39 years, 1725 (73.7%) had sera, and 1425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had lowpositive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]). Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab., Conclusions: High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Endometriosis is a common disease, affecting up to 60-80% of women, with pelvic pain or/and infertility. Despite years of studies, its pathogenesis still remains enigmatic. Genetic, hormonal, environmental, and lifestyle-related factors may be involved in its pathogenesis. Thus, the design of the review was to discuss the possible role of environmental factors in the development of endometriosis. The results of individual studies greatly differ, making it very difficult to draw any definite conclusions. There is no reasonable consistency in the role of environmental factors in endometriosis etiopathogenesis.

Background: Infertility associated with endometriosis can be explained by several non-exclusive mechanisms. The oocyte plays a crucial role in determining embryonic competence and this is particularly relevant for in vitro fertilization (IVF) outcomes. According to some authors, the morphology of oocytes could also be a non-invasive marker of oocyte quality. The aim of this study was to evaluate the relationship between endometriosis and oocyte morphology after controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI) on a large oocyte cohort., Methods: Single-center comparative retrospective study in the academic In Vitro Fertilization (IVF) unit of the Lille University Hospital. A total of 596 women treated for IVF-ICSI with ejaculated spermatozoa for sperm alterations were included. They were classified as endometriosis (n = 175) or control groups (n = 401). The morphological evaluation of 2,016 mature oocytes from 348 cycles of patients with endometriosis was compared with that of 4,073 mature oocytes from 576 control cycles. The main outcome measures were Average Oocyte Quality Index (AOQI) and metaphase II oocyte morphological scoring system (MOMS). Comparison of groups was carried out by a mixed linear model and by a generalized estimation equation model with a "patient" random effect to consider that a patient might have several attempts., Results: No difference in AOQI and MOMS scores was found between endometriosis and control women (adjusted p = 0.084 and 0.053, respectively). In case of endometriosis, there were significantly fewer metaphase II oocytes retrieved, embryos obtained, grade 1 embryos and number of cumulative clinical pregnancies compared to controls. In the endometriosis group, endometriosis surgery was associated with a reduced number of mature oocytes retrieved, and the presence of endometrioma(s) was associated with some abnormal oocyte shapes. Nevertheless, no difference concerning the AOQI and MOMS scores was found in these subgroups., Conclusion: Endometriosis does not have a negative impact on oocytes' morphology in IVF-ICSI., Trial Registration: On December 16, 2019, the Institutional Review Board of the Lille University Hospital gave unrestricted approval for the anonymous use of all patients' clinical, hormonal and ultrasound records (reference DEC20150715-0002)., (© 2021. The Author(s).)

Background: Infertility, an important source of stress, could affect sexual life. Extensive studies suggest that the incidence of sexual dysfunction is highly prevalent in infertile women. As the duration of infertility increases, the level of stress is also likely to increase even further, and this could aggravate psychological pain and cause sexual dysfunction. However, the effect of infertility duration on sexual health is unclear., Methods: We conducted a case-control study in which 715 patients participated between September 1,2020 and December 25, 2020. We included patients diagnosed with infertility (aged between 20 to 45), who were divided into four groups according to their infertility durations: ≤ 2 years (Group I, n = 262), > 2 years but ≤ 5 years (Group II, n = 282), > 5 years but ≤ 8 years (Group III, n = 97), and > 8 years (Group IV, n = 74). A questionnaire survey on female sexual functions and psychological depression was administered to participants, and their female sexual functions and depression status were measured using the Female Sexual Function Index (FSFI) and Patient Health Questionnaire (PHQ-9), respectively., Results: As the number of years of infertility increased, the PHQ-9 score as well as the incidence of psychological depression increased significantly (p < 0.05), but the total score of FSFI and those of its six domains/sub-scales were not significantly different among the four groups. An analysis of the relevant factors affecting sexual functions, using the multivariable logistic regression model, revealed that when the infertility duration was greater than 8 years, there was a significant increase in the incidence of sexual dysfunction [adjusted odds ratios (AOR) = 5.158, 95% confidence interval (CI): 1.935-13.746, P = 0.001], arousal disorder (AOR = 2.955, 95% CI: 1.194-7.314, P = 0.019), coital pain (AOR = 3.811, 95% CI: 1.045-13.897, P = 0.043), and lubrication disorder (AOR = 5.077, 95% CI: 1.340-19.244, P = 0.017)., Conclusions: An increasing infertility duration is a risk factor for the occurrence of sexual dysfunction. Hence, as the infertility duration increases, the incidence of female sexual dysfunction and psychological distress could also increase, especially when the infertility duration is more than 8 years., (© 2021. The Author(s).)

Background: There is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable., Methods: This prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM 2.5 [particulate matter (PM) ≤2.5 μm], PM coarse (PM between 2.5 and 10μm), PM 10 (PM≤10 μm), PM 2.5 abs, and NO 2 and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers., Results: One hundred ninety-four women were recruited, contributing with data for 486 embryo transfers. Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM 2.5 exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM 2.5 , PM coarse and PM 10 on 3D. The second sensitivity analysis showed a significant risk of miscarriage for PM 2.5 exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PM coarse and PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes., Conclusions: Exposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success., (© 2021. The Author(s).)

Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population included women with a diagnosis of SCH or an abnormal thyroid-simulated hormone (TSH) level one year prior to or during pregnancy. We compared characteristics between women who received a prescription for levothyroxine during pregnancy and those who did not. We further described the timing, dose, duration, and temporal trends of levothyroxine prescriptions. Our cohort included 6,757 pregnancies from 6,287 women with SCH, of whom 10% received levothyroxine during pregnancy. Among women who received levothyroxine, most received their first prescription during the first trimester (median gestational age: 7 weeks; interquartile range [IQR]: 0, 16) with a median daily dosage of 50 mcg (IQR: 50, 73). Levothyroxine prescription varied over time, decreasing from 23% of pregnant women in 1998 to 7.5% in 2003, remaining stable until 2014, and increasing to 12.5% in 2016. Smoking, diabetes, polycystic ovary syndrome, infertility, timing of SCH diagnosis, age, TSH level at diagnosis, and general practice regions were associated with prescription. Few women with SCH received levothyroxine during pregnancy, and treatment varied by patient characteristics and geographical regions. These results highlight the need to increase awareness among healthcare providers and will guide future studies that explore barriers to initiating levothyroxine treatment for women with SCH during pregnancy., (© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objective: This study aimed to investigate the effect of ultrasound-diagnosed adenomyosis on assisted pregnancy outcomes, i.e., in vitro fertilization-embryo transfer (IVF-ET)., Methods: This was a retrospective cohort study of 18,568 women who had received their first frozen-thawed ET cycle in Center of Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi and the Reproductive Medicine Center of Tianjin Central Obstetrics and Gynecology Hospital from January 2014 to May 2019. A total of 5,087 patients met the inclusion and exclusion criteria, and they were divided into two groups: adenomyosis with tubal factor infertility (study group, n = 193) and only tubal factor infertility (control group, n = 4894). After a 1:1 propensity score match (caliper value = 0.005), 360 cases were matched in the end., Result: There was no statistical difference in the embryo implantation rate, clinical pregnancy rate, or multiple pregnancy rate between the two groups (28.4% vs. 31.7%, 42.2% vs. 42.8%, and 11.7% vs. 12.8%, respectively; P > 0.05). However, the early miscarriage rate in the adenomyosis group was significantly higher than that in the control group (13.3% vs. 5.6%, respectively; P = 0.012). The live birth rate was 22.8% in the women with adenomyosis and was observed to be significantly lower than 33.3% in the control group (P = 0.026). The patients with adenomyosis had a higher incidence of pregnancy complications than those without (4.4% vs. 0.6%, respectively; P = 0.018), but the neonatal birth weight was not related to adenomyosis., Conclusion: Women with adenomyosis should be treated as being at high risk of early miscarriage. However, maternal adenomyosis has no effect on the birth weight of the newborn., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nearly 14% of US women report any lifetime infertility which is associated with health care costs and psychosocial consequences. Tubal factor infertility (TFI) often occurs as a result of sexually transmitted diseases and subsequent pelvic inflammatory disease. We sought to evaluate for and describe potential racial disparities in TFI and in vitro fertilization (IVF) prevalence., Methods: Records of women aged 19 to 42 years in our retrospective cohort from 2 US infertility clinics were reviewed. We calculated TFI prevalence, IVF initiation prevalence, and prevalence ratios (PRs), with 95% confidence intervals (CIs) for each estimate, overall and by race., Results: Among 660 infertile women, 110 (16.7%; 95% CI, 13.8-19.5%) had TFI which was higher in Black compared with White women (30.3% [33/109] vs 13.9% [68/489]; PR, 2.2 [95% CI, 1.5-3.1]). For women with TFI, IVF was offered to similar proportions of women by race (51.5% [17/33] vs 52.9% [36/68] for Black vs White women); however, fewer Black than White women with TFI started IVF (6.7% [1/15] vs 31.0% [9/29]; PR, 0.2 [95% CI, 0-1.0]), although the difference was not statistically different., Conclusions: Tubal factor infertility prevalence was 2-fold higher among Black than White women seeking care for infertility. Among women with TFI, data suggested a lower likelihood of Black women starting IVF than White women. Improved sexually transmitted disease prevention and treatment might ameliorate disparities in TFI., Competing Interests: Conflicts of Interest: K.R.H. is on the Speakers bureau for AbbVie, and W.M.G. has received research funds and consulting fees from Hologic and consulting fees from Roche. The other authors declare no conflicts of interest., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

The objectives of this study are to assess the prevalence of psychological complaints and changes in sexual function in infertile PCOS women compared with patients with other infertility causes (tubal and male infertility factors) and to identify the predisposing factors. An observational study with three cohorts of infertile women was designed including 37 PCOS patients, 36 women with tubal factor, and 31 women with male factor. Clinical history and physical examination were carried out in all patients. All subjects completed the Hamilton Anxiety Rating Scale, the Beck Depression Inventory, and the Female Sexual Function Index questionnaires. Women with infertility due to PCOS showed a significantly higher prevalence of depressive (48.6 vs 19.4 and 12.9%, p < 0.01) and anxiety symptoms (21.6 vs 5.6 and 3.2%, p = 0.041) than respondents of reference groups. Sexual function in PCOS subjects was impaired in the areas orgasm and satisfaction (p < 0.01 for both) compared to patients of reference groups. Clinical, biochemical hyperandrogenism, and overweight were associated with a higher incidence of depressive and anxiety symptoms in the infertile PCOS group (p < 0.01 for all). Besides, the severity of anxiety symptoms was associated with the number of medically assisted reproduction attempts (p = 0.014). Weight gain and age (p = 0.04 and p = 0.047) were associated with impaired sexual functioning. The relation between reduced sexuality and depressive/anxiety symptoms was found (p = 0.038 and p = 0.012, respectively). Infertile PCOS patients showed the highest prevalence of psychological complaints and some impairment in their sexual functioning. Mental health and sexual functioning need to be part of the routine clinical screening of every PCOS patient. The study was registered at clinicaltrials.gov (identifier: NCT03306459) https://clinicaltrials.gov/ct2/show/NCT03306459?cond=PCOS&cntry=ES&city=Barcelona&draw=2&rank=3., (© 2021. Society for Reproductive Investigation.)

Importance: While surgeons often delay pregnancy and childbearing because of training and establishing early careers, little is known about risks of infertility and pregnancy complications among female surgeons., Objective: To describe the incidence of infertility and pregnancy complications among female surgeons in the US and to identify workplace factors associated with increased risk compared with a sociodemographically similar nonsurgeon population., Design, Setting, and Participants: This self-administered survey questionnaire was electronically distributed and collected from November 2020 to January 2021 through multiple surgical societies in the US and social media among male and female attending and resident surgeons with children. Nonchildbearing surgeons were asked to answer questions regarding the pregnancies of their nonsurgeon partners as applicable., Exposures: Surgical profession; work, operative, and overnight call schedules., Main Outcomes and Measures: Descriptive data on pregnancy loss were collected for female surgeons. Use of assisted reproductive technology was compared between male and female surgeons. Pregnancy and neonatal complications were compared between female surgeons and female nonsurgeon partners of surgeons., Results: A total of 850 surgeons (692 women and 158 men) were included in this survey study. Female surgeons with female partners were excluded because of lack of clarity about who carried the pregnancy. Because the included nonchildbearing population was therefore made up of male individuals with female partners, this group is referred to throughout the study as male surgeons. The median (IQR) age was 40 (36-45) years. Of 692 female surgeons surveyed, 290 (42.0%) had a pregnancy loss, more than twice the rate of the general population. Compared with male surgeons, female surgeons had fewer children (mean [SD], 1.8 [0.8] vs 2.3 [1.1]; P < .001), were more likely to delay having children because of surgical training (450 of 692 [65.0%] vs 69 of 158 [43.7%]; P < .001), and were more likely to use assisted reproductive technology (172 of 692 [24.9%] vs 27 of 158 [17.1%]; P = .04). Compared with female nonsurgeon partners, female surgeons were more likely to have major pregnancy complications (311 of 692 [48.3%] vs 43 of 158 [27.2%]; P < .001), which was significant after controlling for age, work hours, in vitro fertilization use, and multiple gestation (odds ratio [OR], 1.72; 95% CI, 1.11-2.66). Female surgeons operating 12 or more hours per week during the last trimester of pregnancy were at higher risk of major pregnancy complications compared with those operating less than 12 hours per week (OR, 1.57; 95% CI, 1.08-2.26). Compared with female nonsurgeon partners, female surgeons were more likely to have musculoskeletal disorders (255 of 692 [36.9%] vs 29 of 158 [18.4%]; P < .001), nonelective cesarean delivery (170 of 692 [25.5%] vs 24 of 158 [15.3%]; P = .01), and postpartum depression (77 of 692 [11.1%] vs 9 of 158 [5.7%]; P = .04)., Conclusions and Relevance: This national survey study highlighted increased medical risks of infertility and pregnancy complications among female surgeons. With an increasing percentage of women representing the surgical workforce, changing surgical culture to support pregnancy is paramount to reducing the risk of major pregnancy complications, use of fertility interventions, or involuntary childlessness because of delayed attempts at childbearing.

Background: With the prevalence of infertility increasing every year around the world, it has seriously impacted the individual quality of family and social life. Anxiety is one of the most prevalent anxiety disorders among infertile patients. After the two-child policy, whether it affected the prevalence of anxiety is controversial. This study aimed to determine the prevalence of anxiety and its potential risk factors among Chinese infertile women after the enforcement of 'two-child policy'., Methods: This cross-sectional study included 693 infertile patients in a reproductive medical center in Chongqing, China, between February 2016 and December 2018. Data was collected by Self-filling questionnaires including basic demographic information and the Generalized Anxiety Disorder-7 (GAD-7). SPSS statistical software (IBM SPSS version 25) was used to analyse the obtained data. Descriptive analysis was used to describe basic information and anxiety scores, the chi-square test and binary logistic regression were used to analyse the relationship between anxiety and other variables., Results: The prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients (FI), and 18.4% among second-child infertile patients (SI) respectively (P > 0.05). Binary logistic regression showed that patients with lower education levels were more likely to have anxiety (P < 0.01). Patients with middle salary incomes were more likely to have anxiety (OR = 1.860, 95% CI: 1.068-3.238). Oral contraception taking history (OR = 1.778, 95% CI: 1.186-2.667), and history of allergy (OR = 2.098, 95% CI: 1.219-3.612) were associated with anxiety., Conclusions: Under the full liberalization of the "two-child policy", the total prevalence of anxiety among Chinese infertile female is comparatively high. Low education levels, middle incomes, oral contraception taking and allergy history can be the related risk factors of anxiety. We promote that all infertile patients should be evaluated for the prevalence of anxiety, especially those with potential risks, and receive consultant or targeted treatment when needed., (© 2021. The Author(s).)

The present study aimed to assess whether women with polycystic ovarian syndrome (PCOS) ≥35 years age undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles experienced a higher cumulative live birth rate (CLBR) over a two-year period compared with age- and body mass index (BMI)-matched patients with tubal factor infertility. Through propensity score matching (PSM) approach, the authors retrospectively analyzed the IVF/ICSI outcomes of 263 PCOS patients (35-46 years of age [mean, 37 years]) and 526 age- and BMI-matched tubal factor controls two years after oocyte retrieval. Multivariate regression analysis was performed to explore factors influencing cumulative live birth. Women with PCOS exhibited better ovarian reserve and response, and higher CLBR in two years compared with age- and BMI-matched controls (CLBR: 55.51% in PCOS vs . 38.02% in control, p<0.001). Multivariate logistic regression analysis revealed that the number of transferable embryos and antral follicle counts were both significant independent factors predicting cumulative live birth after adjusting for female age, female body mass index, percentage of transferred blastocysts, number of embryos transferred per embryo-transfer cycle, diagnosis of PCOS and freeze-all cycles (p<0.001, p=0.045). Women with PCOS ≥ 35 years of age demonstrated a higher CLBR over two years compared with age- and BMI-matched controls. This could be explained by favorable oocyte reserve and more available embryos compared with controls, which overcome the compromised oocyte quality in aged PCOS patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mai, Liu, Pan, Li, Huang, Chen and Yang.)

Objective: To analyze the correlation between ovarian reserve and thyroid function in women with infertility., Methods: Retrospective analysis of the data of 496 infertility patients who visited the clinic between January 2019 and December 2020. According to the TSH level, it is grouped into <2.5 mIU/L, 2.5~4.0mIU/L and ≥4.0 mIU/L or according to the positive/negative thyroid autoimmune antibody. The relationship was assessed through the ovarian reserve, thyroid function, and anti-Müllerian hormone (AMH) levels in infertile patients. On the other hand, the patients are divided into groups according to age (≤29 years old, 30-34 years old and ≥35 years old), basic FSH (<10 IU/L and ≥10 IU/L), and AMH levels. The ovarian reserve was evaluated through the AMH and the antral follicle count (AFC)., Results: The average age of the patients was 30.31 ± 4.50 years old, and the average AMH level was 5.13 ± 4.30 ng/mL. 3.63% (18/496) of patients had abnormal TSH levels (normal: 0.35-5.5 mIU/L), the positive rate of thyroid peroxidase antibody (TPOAb) was 14.52% (72/496), the positive rate of anti-thyroglobulin antibody (TgAb) was 16.94% (84/496), and the positive rate of TPOAb and TgAb was 10.48% (52/496). After grouping according to TSH level or thyroid autoimmune antibody positive/negative grouping, the analysis found that there was no statistical significance in age, AMH level and basic FSH level among the groups (P>0.05). There were no significant differences in the levels of TSH, FT3, and FT4 among different ages, AMH, and FSH levels (P>0.05)., Conclusion: There is no significant correlation between ovarian reserve and thyroid function in infertile women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Zhao, Wang, Tang and Liu.)

Background: The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status., Methods: Consecutive women ( n = 187) with infertility and RSA, and controls ( n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated., Results: DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency., Conclusion: Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

Objective: To investigate the effects of insulin resistance (IR) on IVF outcomes and a potential underlying mechanism in lean women without PCOS., Design: A prospective cohort study at the University Clinic., Setting: IVF center at the University setting., Patients: A total of 155 lean women (body mass index <25) without PCOS undergoing IVF cycle., Intervention: Patients were allocated to IR and non-IR groups based on HOMA-M 120 ., Main Outcome Measures: IVF outcomes, including egg quality, the percentage of mature oocytes, fertilization rate, blastocyst formation rate, advanced embryo rate, and cumulative live birth rate were investigated. Auto-immune parameters, peripheral blood immunophenotypes, thyroid hormone, homocysteine, and 25-OH-vitamin D 3 (25-OH-VD 3 ) levels were analyzed., Results: The percentage of mature oocytes and blastocyst formation rate were significantly lower in the IR group as compared with those of the non-IR group (p<0.05, respectively). The proportion of peripheral blood CD19 + B cells was significantly higher in the IR group than those of the non-IR group (p<0.05). Homocysteine, 25-OH-VD 3, and auto-immune parameters were the same between the two groups., Conclusion: In lean infertile women without PCOS, IR is associated with the decreased percentage of mature eggs and poor embryo quality in which B cell immunity may play a role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zhang, Fang, Kwak-Kim and Wu.)

Introduction: Genitourinary tuberculosis is the fourth most common cause of extrapulmonary tuberculosis, although often underestimated by clinicians due to its rare and non-specific symptoms. One of the disease's complications is infertility. Although Portugal is one of the European countries with the highest prevalence of tuberculosis, its impact on Portuguese female fertility is unknown. With this study, we intend to evaluate the prevalence of genital tuberculosis, its presenting symptoms, and pregnancy outcomes in infertile women followed in a Portuguese tertiary hospital., Methods: Retrospective and descriptive study, performed using an electronic database and consultation of clinical files. Studied population: infertile women followed from 2000 until 2019 at the reproductive unit of a Portuguese tertiary hospital, who underwent endometrial biopsy/curettage in the context of their etiological investigation. The diagnosis of genital tuberculosis was based on histological criteria., Results: Over the 19 years, 2653 endometrial specimens were analyzed. Pathological evaluation was positive for tuberculosis in 19 cases (0.72%). There was a decrease in new diagnoses throughout the observation period., Conclusion: Despite being one of the European countries with the highest prevalence of tuberculosis, genital TB does not appear to have a significant impact on the etiology of female infertility in Portugal. Nevertheless, it is a diagnosis to be considered in selected patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: To explore the pregnancy outcomes, and neonatal status, arising from embryo transfer in unicornual uterine infertility patients., Methods: We analyzed 2499 cycles of clinical data from in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) from 1st May 2016 to 1st May 2018 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University, including 109 women with unicornuate uterus (the observation group) and 2390 women with normally shaped uterus (the control group)., Results: There were no significant differences in embryo implantation rate, clinical pregnancy rate or miscarriage rate (41.88 % VS 42.36 %, P = 0.904; 48.62 % VS 55.94 %, P = 0.133; 11.01 % VS 8.99 %, P = 0.474) between the two groups. The live birth rate in the observation group was lower than that in the control group (35.78 % VS 45.82 %, P = 0.040). The fetal birth weight of the observation group was lower than that of the control group among single-born live births (3009.12 ± 430.59 g VS 3413.40 ± 492.25 g, P = 0.017), but the differences were not observed in the sex ratio at birth, premature birth rate, low birth weight infant (LBW) rate and macrosomia rate (P > 0.05). The fetal birth weight of the observation group was lower than that of the control group among twins live births (2480.00 ± 190.32 g VS 2606.02 ± 471.59 g), but the difference between the groups did not reach statistical significance (P > 0.05)．Logistic regression analysis showed that age, number of embryos transplanted and uterine morphology were independent influencing factors of live birth., Conclusion: Compared with women with normal uterus, the live birth rate of women with unicornuate uterus is low, and the birth weight of newborns with single birth is reduced., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Research Question: Are there any associations between the variants of FSHR c.2039 G>A (p. Ser680Asn, rs6166) and LHCGR c.935A>G (p. Asn312Ser, rs2293275) and ovarian reserve, ovarian response, clinical pregnancy rate and POSEIDON group?, Design: A total of 210 infertile women were enrolled in this prospective study. The gene variants were analysed by the Sanger method. The clinical parameters were analysed based on genotypes., Results: The frequency of heterozygous and homozygous G allele for FSHR c.2039 G>A in the low prognosis group was significantly higher than that in other response groups (P = 0.034); there was no significant association between LHCGR c.935 A>G and ovarian response. Moreover, the serum anti-Müllerian hormone (AMH) concentration, antral follicle count (AFC), oocytes retrieved, metaphase II (MII) oocytes and two-pronuclear (2PN) oocytes in patients with AG genotype for FSHR c.2039 G>A were significantly lower than those with AA genotype. The serum LH concentrations and clinical pregnancy rate of fresh embryo transfer in patients with GG genotype for LHCGR c.935 A>G were significantly higher than that of the AG genotype. In POSEIDON analysis, the low prognosis women with AA genotype for FSHR c.2039 G>A were more likely to appear in subgroup 1 (P = 0.038)., Conclusion: The FSHR c.2039 G>A variant has a significant beneficial influence on ovarian reserve and ovarian response. The LHCGR c.935 A>G variant is associated with increased clinical pregnancy rate of fresh embryo transfer in infertile women. In addition, the low prognosis women with AA genotype for FSHR c.2039 G>A tend to show better ovarian reserve and prognosis., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. 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.)

Fertility drugs have not definitively been linked to malignant melanoma. By the use of data from a large nationwide cohort of women aged 20.0-45.0 years and living in Denmark between January 1, 1995 and December 31, 2011, we assessed the association between the use of fertility drugs and the risk of malignant melanoma. Information on fertility status and the use of fertility drugs was obtained from the population-based Danish Infertility Cohort. Cox proportional hazard regression models were applied to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. The study population comprised 1,330,954 women, of whom 86,231 (6.5%) were treated with fertility drugs. During a median follow-up of 21.0 years, 6,139 women were diagnosed with malignant melanoma. Compared with fertile women, women with fertility challenges who had used any fertility drugs had an increased risk of malignant melanoma (hazard ratio = 1.14; 95% confidence interval = 1.02-1.27). Furthermore, the use of specific types of fertility drugs (clomiphene, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone preparations, and progesterone) was also associated with an increased risk of malignant melanoma, with hazard ratios ranging between 1.09 and 1.13; however, the association did not reach statistical significance. Our findings indicate that the use of fertility drugs was associated with a modestly increased risk of malignant melanoma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Infertility is associated with increased anxiety, depressive symptoms and mood disorders. Unfortunately, mental health is not often addressed in infertility treatment and infertile patients could be at higher risk of self-administration of not prescribed drugs or/and be exposed to alternative emotional treatments. Therefore, the aim of the present study is to investigate the use of psychotropic medication and to evaluate the frequency of psychiatric diagnosis among infertile women seeking assisted reproductive technology (ART) therapy. Methods All infertile women starting treatment at an ART clinic who agreed to participate in the study were included. Patients were submitted to a structured psychiatric interview, the Mini International Neuropsychiatric Interview (M.I.N.I.). Current and lifetime use of psychotropic medication were assessed. Results Ninety patients who agreed to participate completed the research protocol.  A total of 12/90  were on current use of psychotropic medication.Thirty-six out of ninety patients  had at least one psychiatric disorder. Mood disorders were detected in 19 of the 90. Anxiety disorders were highly frequent, reaching 27/90 of the patients, as agoraphobia the most common diagnosis (12/90). Limitations The study has several limitations, such as the absence of a control group of fertile patients and strict inclusion criteria, in which only subjects that spontaneously agreed to participate were enrolled. Conclusion Women suffering from infertility seeking ART treatment are at high risk for depression and anxiety disorders and a considerable number of them are in use of medication. Its implications on infertility treatments and offspring are uncertain., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To investigate new risk factors for female fertility by analyzing the effects of environmental, social, and surgical factors on antral follicle counts (AFC) and anti-Müllerian hormone (AMH) levels., Methods: A total of 1513 women aged 20-47 years who underwent in vitro fertilization/intracytoplasmic injection treatment in Southwest Hospital from December 2017 to December 2019 were included. Women were assessed for AFC and AMH levels, and completed a questionnaire. Ordinal logistic regression analyses with generalized linear mixed models were used to calculate the adjusted odds ratio (OR) for diminished ovarian reserve., Results: Adnexal surgery was the only risk factor associated with low AFC in women aged 20-30 years. Younger age at menarche, alcohol drinking, and adnexal surgery are three independent risk factors for AMH decline in women aged 20-30 years. Intense exercise, sleep quality, and adnexal surgery are three independent risk factors for a low AFC in women aged 31-36 years. Alcohol drinking and adnexal surgery are two independent risk factors for AMH decline in women aged 31-36 years., Conclusion: With age, female fertility becomes sensitive to high-intensity exercise and poor sleep quality. Adnexal surgery and alcohol drinking are two important risk factors for female fertility in women under age 37 years., (© 2020 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Study Question: Is ICSI better than conventional IVF for non-male factor infertility?, Summary Answer: IVF should be the choice of assisted reproductive technique in non-male factor infertility cases., What Is Already Known: Although total fertilization failure is a major concern for patients and professionals, the overall risk/benefit analysis favors conventional IVF in non-male factor infertility cases. However, according to the ESHRE EIM database pertaining to 1997-2012, the use of IVF has been continuously decreasing in favor of ICSI., Study Design, Size, Duration: Randomized controlled double-blind study involving 138 women undergoing ART in a private Center., Participants/materials, Setting, Methods: All couples with a female partner ≤42 years of age and without severe male factor (total progressive motile sperm with normal morphology >10.000) were included in the study. Exclusion criteria were: history of total fertilization failure, less than 6 cumulus oocyte complexes (COC) available for fertilization, prenatal genetic testing (PGT) cycles, unwillingness to participate and couples undergoing total cryopreservation for any indication. On the day of oocyte pick up, sibling COCs were randomly allocated to fertilization with IVF or denudation followed by ICSI to MII oocytes. The decision to transfer IVF or ICSI embryo(s) depended on embryo quality. Women receiving two embryos were given only IVF or ICSI embryos. Neither the clinician performing the transfer nor the patients were aware of the fertilization method used to generate the embryos transferred. Main outcome parameters were fertilization, clinical pregnancy, implantation and miscarriage rates., Main Results and the Role of Chance: Demographic variables, ovarian reserve and infertility etiology, duration of stimulation, total gonadotropin consumption, peak estradiol levels were similar for IVF-ET and ICSI-ET groups. Mean number of COCs (18.95 vs 19.24), number of embryos transferred (1,81 vs 1,81), the ratio of good quality embryos/total embryos (56.89 % and 55.97 %), clinical pregnancy rates (63 % vs 49 %), implantation rates (31 % vs 28 %), and abortion rates (12,5 % vs 8,1 %) were also similar. A total of 1306 COCs were allocated for IVF while 1331 COCs were denuded for ICSI. Fertilization rate per inseminated oocyte was significantly higher in ICSI group (56,20 % vs 63,78 %). There were ten cases of total fertilization failure, all in the IVF group. Although overall fertilization rate was higher for ICSI, it was similar in both groups when cases with total fertilization failure were excluded., Limitations, Reasons for Caution: The non-availability of live birth rates is a limitation. Randomization of sibling oocytes, not patients requires careful interpretation of pregnancy and implantation rates., Wider Implications of the Findings: Lower cost, ease of application and similar clinical outcome makes IVF the choice of fertilization method in non-male factor infertility cases., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment., Methods: This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher's exact test was used to compare categorical data where appropriate., Results: A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively)., Conclusions: The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment., (© 2021. The Author(s).)

Objective: To examine the association between reproductive factors and risk of non-epithelial ovarian cancer and to compare the associations with those in serous ovarian cancer., Methods: From the Danish Cancer Registry, we identified all ovarian cancer cases (≥20 years old at diagnosis) of germ cell (n = 188), sex cord-stromal (n = 116), or serous (n = 4854) histology during 1982-2016. For each case, 15 age-matched female controls were selected with risk set sampling. Reproductive history was obtained from nationwide registries. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between reproductive factors and the three ovarian cancer types., Results: Compared with nulliparity, ever giving birth was associated with increased odds for germ cell tumors (OR = 1.28, 95% CI: 0.85-1.93) and decreased odds for sex cord-stromal (OR = 0.74, 95% CI: 0.44-1.26) and serous tumors (OR = 0.70, 95% CI: 0.64-0.76). Infertility decreased odds for germ cell tumors (OR = 0.63, 95% CI: 0.23-1.76) but increased odds for sex cord-stromal tumors (OR = 2.20, 95% CI: 0.89-5.43) and serous tumors (OR = 1.97, 95% CI: 1.69-2.30). Finally, use of oral contraceptives decreased the odds for all three tumor types (germ cell: OR = 0.50, 95% CI: 0.29-0.87; sex cord-stromal: OR = 0.40, 95% CI: 0.13-1.22; serous: OR = 0.50, 95% CI: 0.40-0.62)., Conclusions: Reproductive factors affected the risk of sex cord-stromal and serous ovarian cancer similarly with decreased risk associated with parity and use of oral contraceptives. Oral contraceptives also seemed to decrease the risk of germ cell tumors, whereas parity was associated with increased risk., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The present study was undertaken to study time to pregnancy (TTP) and factors associated with TTP in women with axial spondyloarthritis (SpA) compared to women with rheumatoid arthritis (RA)., Methods: We included 274 women with axial SpA and 317 women with RA from the Norwegian nationwide registry RevNatus. For all the women, we had retrospectively collected data on TTP, and a subgroup also had prospectively collected data. We compared TTP in women with axial SpA to women with RA using Kaplan-Meier plots and a log rank test. To identify factors associated with TTP, we used Cox proportional hazards regression., Results: TTP exceeded 12 months in 21% of women with axial SpA. In the subgroup followed prospectively, 32% had TTP that exceeded 12 months. Longer TTP was associated with older age, nulliparity, and longer disease duration, with hazard ratios of 0.97 (95% confidence interval [95% CI] 0.94-1.00), 0.66 (95% CI 0.50-0.88), and 0.94 (95% CI 0.91-0.98), respectively. Disease activity, medication, and self-reported health-related quality of life were not associated with TTP. We found no statistically significant differences between axial SpA and RA in regard to TTP., Conclusion: In women with axial SpA, longer TTP was associated with older age, nulliparity, and longer disease duration., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: A population-based register study utilizing three Finnish National Registers was carried out to determine whether uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis are associated with a subsequent risk of requiring in vitro fertilization (IVF) treatment or a risk of ectopic pregnancy among reproductive-age women., Material and Methods: A total of 23 997 women who underwent appendectomy for uncomplicated or complicated appendicitis or for nonspecific abdominal pain or who had nonspecific abdominal pain without surgical procedures between 2000 and 2012 were included in the study. The later risks of IVF treatment requirement and ectopic pregnancy were assessed after uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis. Women with nonspecific abdominal pain without surgical procedures served as the reference group., Results: The rates of later IVF treatment after uncomplicated appendicitis, complicated appendicitis and appendectomy without appendicitis were low (2.1%, 2.5% and 2.3%, respectively; p = 0.681). Neither appendicitis nor appendectomy was associated with the risk of requiring IVF treatment. The rate of ectopic pregnancy after uncomplicated and complicated appendicitis was very low (0.8%). Women with uncomplicated appendicitis had a significantly lower risk of ectopic pregnancy compared with patients with nonspecific abdominal pain., Conclusions: Appendicitis, whether complicated or uncomplicated, and appendectomy without appendicitis does not increase the risk of requiring later IVF treatment or the risk of ectopic pregnancy., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Background: Infertility is a common gynecological problem in sub-Saharan Africa, including Nigeria. It tends to affect the sexual life of couples and may affect their quality of life., Objective: The study was aimed to assess the impact of infertility on the sexual life of women with infertility seeking care in Enugu, South-East Nigeria., Methods: A questionnaire-based, multicenter cross-sectional study of women with infertility managed at the Gynecology units of the two government-owned tertiary hospitals in Enugu over a 2 months period. The relevant data were obtained and analyzed using SPSS version 20.0., Results: Three hundred and sixty female respondents participated in the study. Their mean age was 35.23 ± 5.7 years. The majority of them were married (98.3%) and attained a tertiary level of education (69%). The number of respondents that reported adequate sexual intercourse dropped from 33.9% before the diagnosis of infertility to 12.2% after the diagnosis. Almost two-thirds of the respondents (65%) reported that they no longer enjoy sex with their husband/partner, whereas 38.9% of them feel they were no longer attracted to their partners., Conclusion: Infertility seems to have a negative effect on the sexual life of women. Addressing this identified negative effect may improve the outcome of infertility management and also may improve the quality of life of women with infertility in the region., Competing Interests: None

Objective: To evaluate the prevalence of endometriosis and peritoneal pockets and to analyze whether these pockets are associated with pain., Methods: Analysis of prospectively registered data of all women undergoing laparoscopy for infertility or pelvic pain between 1988 and 2011 at KU Leuven University Hospital., Results: Of 4497 women, 191 had 238 pockets, with a prevalence of 4.7% in women with infertility only, 4.9% in women with infertility and pelvic pain, and 3.5% in women with pelvic pain only (P = 0.045 for all infertility vs. pelvic pain only). Prevalence did not vary by age. Pockets were associated with endometriosis (P < 0.0001), which was found in 77% of women with pockets. Among women with infertility only, the prevalence of endometriosis was higher in women with pockets (P = 0.0001) than in women without. The prevalence of endometriosis was similar in women with infertility and pelvic pain or pelvic pain only. Pelvic pain as an indication for surgery was associated simultaneously (through logistic regression) with endometriosis (P < 0.0001) and pockets (P = 0.040). Pelvic pain severity was associated simultaneously with pockets (P = 0.0026) and the severity of subtle (P = 0.001), typical (P = 0.030), cystic ovarian (P = 0.051), and deep endometriosis (P < 0.0001). Pelvic pain severity was not associated with endometriosis in the pockets or the diameter or location of pockets., Conclusions: The prevalence of pockets was low, at between 3.5% and 5%. Women with infertility only and pockets had more endometriosis than women without. Severe pelvic pain and pelvic pain as an indication for surgery were associated with the presence of pockets as well as the presence and severity of endometriosis., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.)

Objective: The present study aims to assess the success of controlled ovarian stimulation in intrauterine insemination cycles stimulated by recombinant-FSH and Clomiphene citrate for either mono- or bi-follicular development., Methods: We assessed 870 infertile patients treated with controlled ovarian stimulation in intrauterine insemination cycles at a university-based infertility clinic between January 2012 and December 2017. We compared the cycles stimulated by clomiphene citrate and recombinant-FSH in two set-ups; mono- and bi-follicular development. The main outcome measure was the clinical pregnancy rate per cycle., Results: The demographic and cycle parameters were similar between the groups, except for endometrial thickness on the day of hCG administration, which was higher in the recombinant-FSH group than the clomiphene citrate group. The overall clinical pregnancy rates in clomiphene citrate and recombinant-FSH groups were 9.8% and 10.3%, respectively (p=0.940). Regarding the entire cohort, clinical pregnancy was significantly higher in cases of bi-follicular development when compared to mono-follicular development (16.8% vs. 10.2%, respectively; p=0.009)., Conclusions: Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development. Clomiphene citrate and recombinant-FSH cycles resulted in comparable rates of bi-follicular development, which significantly increases clinical pregnancy rate. Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development.

Persistent high-risk (HR) human papillomavirus (HPV) infection is an essential risk factor for cervical carcinoma and precancerous lesion. There are differences in HPV distribution among different countries, regions and ethnic groups. The aim of this research was to reveal the epidemiological characteristics of HPV in Chongqing, China. In this study, 13,788 women aged 18 to 78 were screened for 23 HPV genotypes by PCR-reverse dot blot hybridization. The total HPV-positive rate was 19.9% (2,745/13,788), while the positive rates for HR, and low-risk (LR) HPV were 17.3% (2,379/13,788), and 4.6% (638/13,788), respectively. In addition to cervical cancer (CC) and cervical intraepithelial neoplasia (CIN) patients, the HPV infection rates among infertile women and women with gynecological diseases were markedly higher than that among healthy women. The HPV and HR-HPV infection rates in the different age groups showed statistically significant differences, and the prevalence peaks were observed in women under 20 years and over 50 years of age. Overall, HPV-52, HPV-16 and HPV-58 ranked as the top 3 most common subtypes among women in Chongqing. The results of this research provide epidemiological information regarding HPV infection in Chongqing. These data constitute valuable evidence for the prevention and management of cervical carcinoma and development of HPV vaccines.

Study Question: Are children of mothers with polycystic ovary syndrome (PCOS) or anovulatory infertility at increased risks of obesity or diabetes?, Summary Answer: Maternal PCOS/anovulatory infertility is associated with an increased risk of offspring obesity from early age and diabetes in female offspring from late adolescence., What Is Known Already: Women with PCOS often have comorbid metabolic disorders such as obesity and diabetes, and children of mothers with PCOS have an increased risk of subtle signs of cardiometabolic alterations., Study Design, Size, Duration: This was a nationwide cohort study of all live births (n = 1 105 997) during 1996-2014 in Finland, excluding those with maternal diagnoses sharing signs and symptoms with PCOS (n = 8244). A total of 1 097 753 births were included and followed up until 31 December 2018., Participants/materials, Setting, Methods: National registries were linked to identify births with maternal PCOS or anovulatory infertility (n = 24 682). The primary outcomes were diagnoses of obesity (ICD-10: E65, E66) and diabetes (ICD-10: E10-E14) in offspring recorded in the Finnish Care Register for Health Care. Cox proportional hazards regression was modeled to analyze the risk of offspring obesity and diabetes in relation to prenatal exposure to maternal PCOS/anovulatory infertility. Differently adjusted models and stratified analyses were used to assess whether the risk was modified by maternal obesity or diabetes diagnoses, pre-pregnancy BMI, fertility treatment or perinatal problems., Main Results and the Role of Chance: Exposure to maternal PCOS/anovulatory infertility was associated with a higher cumulative incidence of obesity in the children (exposed: 1.83%; 95% CI 1.66-2.00% vs unexposed: 1.24%; 95% CI 1.22-1.26%). Accounting for birth factors and maternal characteristics such as obesity and diabetes diagnoses, the hazard ratio (HR) for obesity was increased in offspring below 9 years of age (HR 1.58; 95% CI 1.30-1.81), and in those 10-16 years of age (HR 1.37; 95% CI 1.19-1.57), but not in those aged 17-22 years (HR 1.24; 95% CI 0.73-2.11). Sex-stratified analyses revealed similar risk estimates for boys (HR 1.48; 95% CI 1.31-1.68) and girls (HR 1.45; 95% CI 1.26-1.68). Notably, the joint effect of PCOS/anovulatory infertility and BMI-based pre-pregnancy obesity on offspring obesity (HR 8.89; 95% CI 7.06-11.20) was larger than that of either PCOS/anovulatory infertility or obesity alone. Furthermore, PCOS/anovulatory infertility was associated with offspring obesity in children without perinatal problems (HR 1.27; 95% CI 1.17-1.39), with larger effect size for maternal PCOS/anovulatory infertility and joint perinatal problems (HR 1.61; 95% CI 1.35-1.91). However, the risk estimates were comparable between maternal PCOS/anovulatory infertility with (HR 1.54; 95% CI 1.17-2.03) and without fertility treatment (HR 1.46; 95% CI 1.32-1.61). For offspring diabetes, the HR was increased only between 17 and 22 years of age (HR 2.06; 95% CI 1.23-3.46), and specifically for Type 1 diabetes in females (HR 3.23; 95% CI 1.41-7.40)., Limitations, Reasons for Caution: The prevalence of PCOS/anovulatory infertility in this study was 2.2%, lower than that reported in previous studies. In addition, the incidence of obesity in offspring was lower than that reported in studies based on measured or self-reported weight and height and may include mainly moderate and severe obesity cases who needed and/or actively sought medical care. Moreover, mothers with PCOS/anovulatory infertility were identified based on ICD codes, with no information on PCOS phenotypes. Furthermore, maternal pre-pregnancy BMI was available only from 2004. The PCOS/anovulatory infertility association with female offspring diabetes was based on only a few cases. Mothers' weight gain during pregnancy, use of fertility treatment other than fresh or frozen IVF/ICSI, offspring lifestyle, as well as fathers' age, medical disorders or medication prescriptions were not available for this study., Wider Implications of the Findings: These findings support that prenatal PCOS/anovulatory infertility exposure influences metabolic health in the offspring from early age., Study Funding/competing Interest(s): This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], Shandong Province Medical and Health Technology Development Plan [2018WS338 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and Pregnancy Project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 and SLL20190589 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: The COVID-19 pandemic has implied worldwide the imposition of confinement measures and mobility restrictions, to a greater or lesser extent. It has also meant the closure of some public medical services such as reproductive care. This situation may have impacted the health-related behaviour and quality of life of women with fertility problems. Objective: The objective of this study was to analyse the effects of confinement and the suspension of reproductive medical care on the lifestyle (diet, physical exercise, and smoking habits), anxiety and depression, and quality of life of infertile women by comparing their pre- and post-confinement situations. Methods: We carried out a cross-sectional, internet-based study. Information was collected on these women's adherence to the Mediterranean diet (MEDAS questionnaire), physical exercise (IPAQ-SF), anxiety and depression (HADS), and quality of life related to fertility (FertiQol) before, during, and after confinement. The survey was conducted between 1 September and 28 October 2020. Results: A total of 85 women participated. There had been a significant increase in anxiety and depression levels ( P < 0.001) and an increase in tobacco consumption among female smokers during confinement vs. pre-confinement (62.5% had increased their consumption). The participants had also increased the mean number of hours they spent sitting ( P < 0.001). There had also been an increase in vigorous and moderate exercise levels by 40 and 30%, respectively ( P = 0.004). However, no differences were observed in these patients' eating habits as a result of confinement ( P = 0.416). When the reproduction service was resumed, the participants showed higher anxiety level scores ( P = 0.001) with respect to the pre-confinement situation as well as lower mean FertiQol scale score ( P = 0.008). Conclusions: Confinement had increased anxiety and depression levels among these infertile women as well as tobacco use among the participants who were smokers. The prolonged closure of reproductive care units decreased the quality of life of the participants of this study. These results suggest the need to implement online programs to improve healthy habits and quality of life of this population group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Biviá-Roig, Boldó-Roda, Blasco-Sanz, Serrano-Raya, DelaFuente-Díez, Múzquiz-Barberá and Lisón.)

Several studies have reported the association between thyroid autoimmunity (TAI) and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes. However, the findings remain controversial. We performed a large-scale retrospective cohort study to verify the effect of the presence of thyroid antibodies on IVF/ICSI outcomes and fetal growth and to evaluate the association between the types and titers of thyroid antibodies and adverse IVF/ICSI outcomes. A total of 16481 patients with infertility were referred to the Reproductive Center of Peking University Third Hospital for their first IVF/ICSI treatment between January 2018 and June 2019.Patients who sought IVF/ICSI treatment due to tubal or male factors infertility and who achieved fresh embryo transfer were included in our study. Finally, 778 patients with thyroid antibody positivity were selected as the TAI group, and 778 age-matched patients were included in the control group. The number of oocytes retrieved and high-graded embryos and the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were compared between the TAI and control groups. In addition, subgroup analysis was performed to demonstrate whether different types and titers of thyroid antibodies had different effects on IVF/ICSI outcomes. After adjusting for thyroid function, anti-Müllerian hormone levels, basal follicle stimulating hormone levels, basal estradiol levels and antral follicle count, the number of oocytes retrieved in the TAI group was significantly lower than that in the control group. No significant differences were observed between the two groups in the rates of clinical pregnancy, miscarriage, preterm delivery, live birth, and birth weight in singletons; however, the birth weight in twin pregnancy was significantly lower in the TAI group than in the control group. Subgroup analysis showed no association between the types or titers of thyroid antibodies and adverse IVF/ICSI outcomes. In conclusion, the presence of TAI in patients with infertility did not impair embryo quality or affect pregnancy outcomes, including clinical pregnancy, miscarriage, preterm delivery, and live birth. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Chen, Lian, Wang, Li, Qiao and Chi.)

Background: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease., Objective: This study aimed to examine the association between female infertility and all-cause mortality., Study Design: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race., Results: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone., Conclusion: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Infertility is a public health challenge and it is a distressing personal tragedy for couples, more so for the female partners. Risk factors and causes of infertility vary from region to region. Reactive species is of current interest in the pathogenesis and management of infertility, especially in the Niger-Delta Region of Nigeria where environmental hazards of oil exploration exists., Aim: The overall goal of this study was to determine and compare the serum reactive species levels (nitric oxide) in fertile and infertile women attending the infertility clinic at the Delta State University Teaching Hospital, Oghara, and Central Hospital, Warri., Methods: This was a prospective case-control study in which 70 women evaluated for infertility were recruited into the study. A fertile patient matched for age and body mass index (BMI) attending family planning clinic was selected as control. Serum nitric oxide estimation was done using the BioVision Nitric Oxide Colorimetric Assay Kit. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS). Student's t-test was applied to compare the serum levels of nitric acid and the differences were considered significant if P < 0.05., Results: Infertile women had significantly higher mean serum nitric oxide levels than fertile women: 34.33 (SD 5.93) μmol/L versus 18.27 (SD 2.63) μmol/L (P < 0.001). Women with secondary infertility had significantly higher mean levels of nitric oxide than those with primary infertility: 38.13 (SD 3.39) μmol/L versus 22.72 (SD 4.36) μmol/L (P < 0.001)., Conclusion: The study showed that serum nitric oxide level was significantly elevated in women with infertility compared to women of proven fertility. Hence, oxidative stress from reactive species may be a contributory factor to infertility in women in the Niger-Delta Region of Nigeria., Competing Interests: None

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.

Objective: To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Women without any previous history of breast cancer undergoing ovarian stimulation., Intervention(s): Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls., Main Outcome Measure(s): New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs., Result(s): Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I 2 = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination., Conclusion(s): The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with endometriosis may seek traditional Chinese medicine (TCM) to help them conceive. The present study aims to evaluate the effects of TCM on reproductive and pregnancy outcomes in patients with endometriosis., Materials and Methods: The patients with endometriosis taken from the National Health Insurance (NHI) research database between 2000 and 2012 were divided into two cohorts based on the use of TCM treatment. The two cohorts were matched by age and comorbidities and followed up until a new diagnosis of infertility, ectopic pregnancy, or miscarriage. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of reproductive and pregnancy outcomes., Results: A total of 5244 patients with endometriosis were analyzed, including 1748 TCM users and 3496 matched control subjects. The proportion of infertility was higher in TCM users than in non-TCM users (adjusted hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 1.13-1.60). However, there was no significant difference in the proportion of ectopic pregnancies between TCM users and non-TCM users (adjusted HR: 0.82, 95% CI: 0.60-1.13). There was no significant difference in the proportion of miscarriages between TCM users and non-TCM users (adjusted HR: 1.23, 95% CI: 0.95-1.61)., Conclusion: TCM treatment showed insignificant efficacy in decreasing the risk of ectopic pregnancy and miscarriage in patients with endometriosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.)