Showing papers on "Fertility published in 2022"

OUP accepted manuscript

Abstract: What is the impact of adenomyosis on the live birth rate (LBR) in women affected by endometriosis women undergoing ART?For women undergoing ART, the presence of adenomyosis at MRI, especially T2 high-signal intensity spots within the myometrium, has a negative impact on the LBR.Adenomyosis is a common gynecological disease. The development of imaging techniques for the diagnosis has led to several adenomyosis phenotypes being described, and fertility issues appear to vary according to the characteristics of the lesions. What makes assessment of the impact of adenomyosis on fertility issues even more difficult is its frequent association with endometriosis, which is another known risk factor of infertility. Although data suggest that adenomyosis may worsen the ART prognosis, there is no clear consensus regarding the impact of adenomyosis on ART outcomes in women affected by endometriosis.This was an observational study that included phenotyped patients with endometriosis, aged between 18 and 42 years, who underwent IVF/ICSI treatment in a tertiary care center between June 2015 and July 2018. Only women who had undergone a pelvic MRI during the pre-therapeutic ART workup were retained for this study. The MRI data were interpreted by radiologists who had expertise in gynecological MRI.A continuous series of 202 women affected by endometriosis was included. The women were monitored until four ART cycles had been completed, until delivery, or until discontinuation of treatment before the completion of four cycles. The primary outcome was the delivery of at least one live infant after up to four IVF/ICSI cycles. The patient and the MRI characteristics were compared between the women who achieved a live birth versus those who did not.The patients' mean age was 32.5 ± 3.7 years. Deep infiltrating endometriosis was present in 90.1% (182/202) of the included population. Adenomyosis (lesions of the internal and/or the external myometrium) was found in 71.8% (145/202) of the included women. The cumulative LBR was 57.4% (116/202). The women who gave birth were significantly younger (32.0 ± 3.3 versus 33.3 ± 4.1, P = 0.026) and had significantly better ovarian reserve parameters (anti-Müllerian hormone levels, antral follicle count) than those who did not. The presence of adenomyosis, irrespective of the phenotype (76/116 (65.5%) versus 69/86 (80.2%), respectively, P = 0.022) and the presence of T2 high-signal intensity myometrial spots (27/116 (23.3%) and 37/86 (43.0%), respectively, P = 0.003) was significantly less frequent in the group of women who gave birth versus those who did not. After multivariate analysis, the presence of adenomyosis (odds ratio (OR): 0.48, 95% CI (0.29-0.99), P = 0.048) and the presence of T2 high-signal intensity myometrial spots (OR: 0.43, 95% CI (0.22-0.86), P = 0.018) were independently found to be associated with a decrease in the cumulative chance of live birth.The inclusion of patients from a referral center specialized in the management of women affected by endometriosis could constitute a selection bias, as these women may have had particularly severe forms of adenomyosis and/or endometriosis. A sensitive issue is that there is no consensual classification of adenomyosis and several lesions of adenomyosis can co-exist. Therefore, a comparison of fertility outcomes between women with and without adenomyosis is difficult to perform in practice.In women exhibiting endometriosis, the practitioner should perform an appropriate imaging workup to search for adenomyosis, identify prognostic factors, and personalize the patient management strategy in the setting of ART.No funding was obtained and there were no conflicts of interest.N/A.

A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility

Abstract: Abstract Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21–45 year residing in the United States or Canada during December 2020–September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.

OUP accepted manuscript

Abstract: Abstract Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21–45 year residing in the United States or Canada during December 2020–September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.

ART in Europe, 2018: results generated from European registries by ESHRE

Abstract: Abstract STUDY QUESTION What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2018 as compared to previous years? SUMMARY ANSWER The 22nd ESHRE report shows a continued increase in reported numbers of ART treatment cycles and children born in Europe, a decrease in transfers with more than one embryo with a further reduction of twin delivery rates (DRs) as compared to 2017, higher DRs per transfer after fresh IVF or ICSI cycles (without considering freeze-all cycles) than after frozen embryo transfer (FET) with higher pregnancy rates (PRs) after FET and the number of reported IUI cycles decreased while their PR and DR remained stable. WHAT IS KNOWN ALREADY ART aggregated data generated by national registries, clinics or professional societies have been gathered and analysed by the European IVF-monitoring Consortium (EIM) since 1997 and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE on a yearly basis. The data on treatment cycles performed between 1 January and 31 December 2018 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons of 39 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1422 clinics offering ART services in 39 countries reported a total of more than 1 million (1 007 598) treatment cycles for the first time, including 162 837 with IVF, 400 375 with ICSI, 309 475 with FET, 48 294 with preimplantation genetic testing, 80 641 with egg donation (ED), 532 with IVM of oocytes and 5444 cycles with frozen oocyte replacement (FOR). A total of 1271 institutions reported data on IUI cycles using either husband/partner’s semen (IUI-H; n = 148 143) or donor semen (IUI-D; n = 50 609) in 31 countries and 25 countries, respectively. Sixteen countries reported 20 994 interventions in pre- and post-pubertal patients for FP including oocyte, ovarian tissue, semen and testicular tissue banking. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries (21 in 2017) in which all ART clinics reported to the registry, 410 190 treatment cycles were registered for a total population of ∼ 300 million inhabitants, allowing a best estimate of a mean of 1433 cycles performed per million inhabitants (range: 641–3549). Among the 39 reporting countries, for IVF, the clinical PR per aspiration slightly decreased while the PR per transfer remained similar compared to 2017 (25.5% and 34.1% in 2018 versus 26.8% and 34.3% in 2017). In ICSI, the corresponding rates showed similar evolutions in 2018 compared to 2017 (22.5% and 32.1% in 2018 versus 24.0% and 33.5% in 2017). When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.8% (29.4% in 2017) and 27.3% (27.3% in 2017) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was 33.4% (versus 30.2% in 2017), and with embryos originating from donated eggs 41.8% (41.1% in 2017). After ED, the PR per fresh embryo transfer was 49.6% (49.2% in 2017) and per FOR 44.9% (43.3% in 2017). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 50.7%, 45.1%, 3.9% and 0.3% of all treatments, respectively (corresponding to 46.0%, 49.2%. 4.5% and 0.3% in 2017). This resulted in a reduced proportion of twin DRs of 12.4% (14.2% in 2017) and similar triplet DR of 0.2%. Treatments with FET in 2018 resulted in twin and triplet DRs of 9.4% and 0.1%, respectively (versus 11.2% and 0.2%, respectively in 2017). After IUI, the DRs remained similar at 8.8% after IUI-H (8.7% in 2017) and at 12.6% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%), and 6.4% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). Among 20 994 FP interventions in 16 countries (18 888 in 13 countries in 2017), cryopreservation of ejaculated sperm (n = 10 503, versus 11 112 in 2017) and of oocytes (n = 9123 versus 6588 in 2017) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION The results should be interpreted with caution as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 22nd ESHRE data collection on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts towards optimization of both the collection and reporting, with the aim of improving surveillance and vigilance in the field of reproductive medicine, are awaited. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries.

Abstract: BACKGROUND Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America-Europe-Australia (NEA) based on studies published during 1981-2013. At that time, there were too few studies with data from South/Central America-Asia-Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014-2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973-2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: -0.87 million/ml/year, 95% CI: -0.89 to -0.86; P < 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (-1.27; -1.78 to -0.77; P < 0.001) and unselected men from SAA (-0.65; -1.29 to -0.01; P = 0.045) and fertile men from NEA (-0.50; -1.00 to -0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (-1.17: -1.66 to -0.68; P < 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (-1.73: -3.23 to -0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (-4.70 million/year; -6.56 to -2.83; P < 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS This analysis is the first to report a decline in sperm count among unselected men from South/Central America-Asia-Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.

Country-specific estimates of unintended pregnancy and abortion incidence: a global comparative analysis of levels in 2015–2019

Abstract: Introduction Internationally comparable estimates of unintended pregnancy and abortion incidence can illuminate disparities in sexual and reproductive health and autonomy. Country-specific estimates are essential to enable international comparison, and to inform country-level policy and programming. Methods We developed a Bayesian model which jointly estimated unintended pregnancy and abortion rates using information on contraceptive needs and use, contraceptive method mix, birth rates, the proportions of births from unintended pregnancies and abortion incidence data. Main outcomes were the estimated rates of unintended pregnancy and abortion for 150 countries and territories, reported for the 5-year period 2015–2019, as annual averages per 1000 women aged 15–49 years. Results Estimated unintended pregnancy rates ranged from 11 (80% uncertainty interval: 9 to 13) in Montenegro to 145 (131 to 159) in Uganda per 1000 women aged 15–49 years. Between-country heterogeneity was substantial in all Sustainable Development Goal (SDG) regions, but was greatest in sub-Saharan Africa. Estimated abortion rates ranged from 5 (5 to 6) in Singapore to 80 (55 to 113) in Georgia. Variation between country estimates was similar in all SDG regions except for Europe and Northern America, where estimated abortion rates were generally lower. Conclusion The estimates reflect variation in the degree to unintended pregnancy and abortion that are experienced in countries throughout the world. This evidence highlights the importance of investing in access to contraception and comprehensive abortion care, including in regions which may have lower rates of unintended pregnancy or abortion, respectively, as countries may differ substantially from regional averages.

The Effects of SARS-CoV-2 Infection on Female Fertility: A Review of the Literature

Abstract: As the coronavirus pandemic is far from ending, more questions regarding the female reproductive system, particularly fertility issues, arise. The purpose of this paper is to bring light upon the possible link between COVID-19 and women’s reproductive health. This review emphasizes the effect of SARS-CoV-2 on the hormones, endometrium and menstrual cycle, ovarian reserve, follicular fluid, oocytes, and embryos. The results showed that endometrial samples did not express SARS-CoV-2 RNA. Regarding the menstrual cycle, there is a large range of alterations, but they were all reversible within the following months. The ovarian reserve was not significantly affected in patients recovering from both mild and severe infection in most cases, except one, where the levels of AMH were significantly lower and basal follicle-stimulating hormone (FSH) levels were increased. All COVID-19 recovered patients had positive levels of SARS-CoV-2 IgG in the follicular fluid. The amount of retrieved and mature oocytes and the fertilization rate were unharmed in three studies, except for one study, where the quantity of retrieved and mature oocytes was reduced in patients with higher levels of SARS-CoV-2 antibodies. The numbers of blastocysts, top-quality embryos, and euploid embryos were affected in most of the studies reviewed.

Root exudates shift how N mineralization and N fixation contribute to the plant-available N supply in low fertility soils

Abstract: Nitrogen (N) availability is a primary constraint to plant productivity, especially in marginal lands with inherently low fertility. Root exudates change with plant nutrient status, and are expected to affect the microbially-mediated N transformations (gross N mineralization vs N fixation) in low fertility soil (low soil organic matter). To explore this possibility, we sampled soils from two monoculture switchgrass (var. Cave-In-Rock ) plot with and without N addition at two marginal land sites in Michigan, USA. In a two-week lab incubation, we quantified the effect of different root exudates on gross N mineralization and N fixation by adding simulated root exudates (carbohydrates, organic acids) at a rate of 100 μg C g −1 day −1 . On average, adding carbohydrates to low fertility soil increased the soil respiration by 254%, the dissolved organic carbon (DOC) by 366% and reduced dissolved organic N (DON) by 40%. In contrast, soils receiving organic acids had 159% more soil respiration, 163% higher DOC concentration and the DON concentration increased by 49%. Analysis of the C recovery in measured pools revealed that root exudates C inputs were nearly equivalent to the DOC, microbial biomass carbon (MBC), and soil respiration in sandy soil, but only 45–74% of the root exudate C was recovered in these pools in the sandy loam soil. This suggests that root exudate C may be adsorbed to mineral particles in the sandy loam soil. Soil treated with organic acids had higher gross N mineralization and N immobilization rates than soil with carbohydrates addition. Adding carbohydrates significantly increased the free-living N fixation rates, compared to organic acid addition. Changes in soil pH, and DON induced by root exudate addition had strong association with N transformation rates and N availability. Gross N mineralization produced more plant-available N than N fixation, as evidenced by higher inorganic N concentration in soils receiving organic acids than carbohydrates. By quantifying how different root exudates affect the contribution of N mineralization and N fixation to the plant-available N pool in low fertility soils, this study enhances our understanding of the “C for N” exchange in the plant rhizosphere. Conceptual diagram showed potential mechanisms of root exudates (organic acids versus carbohydrates) on different N transformation processes in rhizosphere under different N conditions . DOC: dissolved organic carbon; DON, dissolved organic nitrogen; MBC, microbial biomass carbon. Note that plant excrete more organic acids under N limiting condition, whereas more carbohydrates without N limitation (Smercina et al., 2020a). Compared with carbohydrates addition, organic acids significantly increased soil pH, which induced release of mineral-associated organic matter and increased DON that in turn shift how N mineralization and N fixation contribute to plant available N in low fertility soils. While carbohydrates addition significantly increased soil respiration, which depleted DOC and DON, the decrease DON therefore decrease the N mineralization but increase the N fixation. • Carbohydrates addition increased soil N fixation relative to N mineralization. • Organic acids addition increased soil N mineralization relative to N fixation. • Organic acids addition significantly increased DON in Lake City soils. • Legacy of N addition had no effects on either N mineralization or N fixation. • Changes in soil pH and DON drive the change of N availability.

Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

Abstract: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters?A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology.The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO.The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review

Abstract: Endometrial cancer occurs in up to 29% of women before 40 years of age. Seventy percent of these patients are nulliparous at the time. Decision making regarding fertility preservation in early stage endometrial cancer (ES-EC) is, therefore, a big challenge since the decision between the risk of cancer progression and a chance to parenthood needs to be made. Sixty-two percent of women with complete remission of ES-EC after fertility-sparing treatment (FST) report to have a pregnancy wish which, if not for FST, they would not be able to fulfil. The aim of this review was to identify and summarise the currently established biomolecular and genetic prognostic factors that can facilitate decision making for FST in ES-EC. A comprehensive search strategy was carried out across four databases; Cochrane, Embase, MEDLINE, and PubMed; they were searched between March 1946 and 22nd December 2022. Thirty-four studies were included in this study which was conducted in line with the PRISMA criteria checklist. The final 34 articles encompassed 9165 patients. The studies were assessed using the Critical Appraisal Skills Program (CASP). PTEN and POLE alterations we found to be good prognostic factors of ES-EC, favouring FST. MSI, CTNNB1, and K-RAS alterations were found to be fair prognostic factors of ES-EC, favouring FST but carrying a risk of recurrence. PIK3CA, HER2, ARID1A, P53, L1CAM, and FGFR2 were found to be poor prognostic factors of ES-EC and therefore do not favour FST. Clinical trials with bigger cohorts are needed to further validate the fair genetic prognostic factors. Using the aforementioned good and poor genetic prognostic factors, we can make more confident decisions on FST in ES-EC.

Assisted Reproductive Technology Surveillance — United States, 2018

Abstract: Problem/Condition Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple births because multiple embryos might be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2018 and compares birth outcomes that occurred in 2018 (resulting from ART procedures performed in 2017 and 2018) with outcomes for all infants born in the United States in 2018. Period Covered 2018. Description of System In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102–493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 U.S. states, the District of Columbia, and Puerto Rico. Results In 2018, a total of 203,119 ART procedures (range: 196 in Alaska to 26,028 in California) were performed in 456 U.S. fertility clinics and reported to CDC. These procedures resulted in 73,831 live-birth deliveries (range: 76 in Puerto Rico and Wyoming to 9,666 in California) and 81,478 infants born (range: 84 in Wyoming to 10,620 in California). Nationally, among women aged 15–44 years, the rate of ART procedures performed was 3,135 per 1 million women. ART use exceeded 1.5 times the national rate in seven states (Connecticut, Illinois, Maryland, Massachusetts, New Jersey, New York, and Rhode Island) and the District of Columbia. ART use rates exceeded the national rate in an additional seven states (California, Delaware, Hawaii, New Hampshire, Utah, Vermont, and Virginia). Nationally, among all ART transfer procedures, the average number of embryos transferred was similar across age groups (1.3 among women aged <35 years, 1.3 among women aged 35–37 years, and 1.4 among women aged >37 years). The national single-embryo transfer (SET) rate among all embryo-transfer procedures was 74.1% among women aged <35 years (range: 28.2% in Puerto Rico to 89.5% in Delaware), 72.8% among women aged 35–37 years (range: 30.6% in Puerto Rico to 93.7% in Delaware), and 66.4% among women aged >37 years (range: 27.1% in Puerto Rico to 85.3% in Delaware). In 2018, ART contributed to 2.0% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.1% in Massachusetts) from procedures performed in 2017 and 2018. Approximately 78.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 12.5% of all multiple births, including 12.5% of all twin births and 13.3% of all triplets and higher-order births. ART-conceived twins accounted for approximately 97.1% (15,532 of 16,001) of all ART-conceived multiple births. The percentage of multiple births was higher among infants conceived with ART (21.4%) than among all infants born in the total birth population (3.3%). Approximately 20.7% (15,532 of 74,926) of ART-conceived infants were twins, and 0.6% (469 of 74,926) were triplets and higher-order multiples. Nationally, infants conceived with ART contributed to 4.2% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 18.3% were low birthweight compared with 8.3% among all infants. ART-conceived infants contributed to 5.1% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (26.1%) than among all infants born in the total birth population (10.0%). The percentage of low birthweight among singletons was 8.3% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.9% compared with 8.3% among all singleton infants. The percentages of small for gestational age infants was 7.3% among ART-conceived infants compared with 9.4% among all infants. Interpretation Although singleton infants accounted for the majority of ART-conceived infants, multiple births from ART varied substantially among states and nationally, contributing to >12% of all twins, triplets, and higher-order multiple infants born in the United States. Because multiple births are associated with higher rates of prematurity than singleton births, the contribution of ART to poor birth outcomes continues to be noteworthy. Although SET rates increased among all age groups, variations in SET rates among states and territories remained, which might reflect variations in embryo-transfer practices among fertility clinics and might in part account for variations in multiple birth rates among states and territories. Public Health Action Reducing the number of embryos transferred and increasing use of SET, when clinically appropriate, can help reduce multiple births and related adverse health consequences for both mothers and infants. Whereas risks to mothers from multiple-birth pregnancy include higher rates of caesarean delivery, gestational hypertension, and gestational diabetes, infants from multiple births are at increased risk for numerous adverse sequelae such as preterm birth, birth defects, and developmental disabilities. Long-term follow-up of ART infants through integration of existing maternal and infant health surveillance systems and registries with data available from NASS might be useful for monitoring adverse outcomes on a population basis.

China’s fertility change: an analysis with multiple measures

Abstract: The period fertility in China has declined to very low levels, and the completed cohort fertility rate (CFR) has also decreased significantly. However, the exact fertility rate remains controversial. While the tempo effect has played a significant role in China's period fertility decline, child underreporting has to be taken into consideration in China's fertility research.By using the census data from 1982 to 2010, and the 1% population sample survey data from 1995 to 2015, we systematically analyzed China's fertility and its trends since the 1980s using period fertility measures, adjusted period fertility measures, cohort fertility measures, and indirect estimation methods.The results show that marriage postponement significantly affects the TFR decline. Even after eliminating the tempo and parity structure effect, the adjusted TFR has fallen below 1.5, and the first-order fertility rate dropped to 0.9 in 2015. The CFR for women aged 45-49 declined from 5.37 in 1982 to 1.62 in 2015 mainly because of a decrease in fourth and higher-order births from 1982 to 1990, a decrease in second and third births from 1990 to 2000, and a decrease in second births from 2000 to 2015. Indirect estimation methods yielded a TFR in the range of 1.5-1.6 for the period 2000-2010 and an average TFR of 1.49 for the period 2011-2020.The traditional norm of universal marriage and childbearing for Chinese women is changing. China's fertility has been steadily declining, as measured by both period and cohort indicators. Following the historical change, fertility may continue to decline even after introducing the universal three-child policy in China in 2021.

Advanced Deep Learning Human Herpes Virus 6 (HHV-6) Molecular Detection in Understanding Human Infertility

Abstract: To see if HHV-6 may be a cause of infertility, researchers looked at 18 men and 10 women who had unexplained critical fertility and had at least one prior pregnancy. HHV-6 DNA was discovered in both infertile and fertile peripheral blood mononuclear cells (PBMC) (12 and 14%, respectively); endometrial epithelial cells from 4/10 (40%) infertile women were positive for HHV-6 DNA; this viral DNA was not found in the endometrium of fertile women. When endometrial epithelial cells were cultivated, they produced viral early and late proteins, suggesting the existence of an infectious virus. Endometrial HHV-6 infection creates an aberrant NK cell and cytokine profile, resulting in a uterine domain that is not favorable to conception, according to the findings. To corroborate the findings, studies of extra fertile and barren women should be done. Semen samples were taken from 18 guys who visited the Government General Hospital Guntur's infertility department because they were having reproductive issues with their partners. Herpes virus DNA has been discovered in the sperm of symptomatic fertile and infertile male patients on rare instances. Furthermore, researchers must investigate the role of viral diseases in male infertility.

The Endometrial Microbiome and Its Impact on Human Conception

Abstract: Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.

Impact of environmental factors on human semen quality and male fertility: a narrative review

Abstract: Abstract Background Worldwide rising trend in infertility has been observed in the past few years with male infertility arising as a major problem. One main reason for the rise in male infertility cases is declining semen quality. It was found that any factor that affects semen quality can affect male fertility. There are several modifiable factors affecting semen quality including air pollution, use of pesticides and harmful chemicals, exposure to excessive heat, and can lead to decreased male fertility. Main body The present review focuses on some of these environmental factors that affect semen quality and hence, can cause male infertility. The literature from 2000 till June 2021 was searched from various English peer-reviewed journals and WHO fact sheets using the USA National Library of Medicine (PubMed) database, the regional portal of Virtual Health Library, and Scientific Electronic Library Online. The search terms used were: “Air pollution and male fertility”, “Chemicals and male infertility”, “Heat exposure and infertility”, “heavy metals and male fertility”. Conclusion Adverse environmental factors have a significant impact on semen quality, leading to decreased sperm concentration, total sperm count, motility, viability, and increased abnormal sperm morphology, sperm DNA fragmentation, ultimately causing male infertility. However, all these factors are modifiable and reversible, and hence, by mere changing of lifestyle, many of these risk factors can be avoided.

The impact of COVID-19 on fertility behaviour and intentions in a middle income country

Abstract: The COVID Pandemic may affect fertility behaviour and intentions in many ways. Restrictions on service provision reduce access to family planning services and increase fertility in the short term. By contrast, the economic uncertainty brought about by the pandemic and its impact on mental health and well-being may reduce fertility. These various pathways have been explored in the context of high income countries such as the United States and Western Europe, but little is known about middle income countries. In this paper we asses the impact of the COVID pandemic on fertility intentions and behaviour in the Republic of Moldova, a middle income country in Eastern Europe, using the Generations and Gender Survey. This survey was conducted partially before and partially after the onset of the pandemic in 2020, allowing for detailed comparisons of individual circumstances. The results indicate that the pandemic reduced the used of intrauterine devices, and increased the use of male condoms, but with no overall decrease in contraceptive use. Conversely individuals interviewed after the onset of the pandemic were 34.5% less likely to be trying to conceive, although medium term fertility intentions were unchanged. Indicators therefore suggest that in the medium term fertility intentions may not be affected by the pandemic but restricted access to contraception requiring medical consultation and a decrease in short-term fertility intentions could disrupt short term family planning.

COVID-19 Vaccination Does Not Affect Reproductive Health Parameters in Men

Abstract: With the implementation of COVID-19 vaccine up-take, doubts regarding the impact of immunization on future fertility have begun to emerge. We have examined vaccine safety on male reproductive health. We set up a multicentre (three infertility centers), retrospective study in order to assess semen parameters and fertilization rate of one hundred-six men in a pairwise comparison between the first and second assisted reproduction technology (ART) attempt, performed respectively before and after COVID-19 vaccination. Median time (range) between the first vaccine dose and the second ART cycle was 75 days (39–112). Semen parameters did not change before and after the exposure. Fertilization rate was also similar before and after vaccination. Twenty-five patients (24%) were oligozoospermic before the vaccination while 26 (25%) after the exposure (P = 0.87). Severe asthenozoospermia were present in 11 patients before as well as after the exposure. No difference was observed even after considering different types of vaccines (mRNA or viral vector). COVID-19 vaccination did not affect sperm quality and fertilization capacity of men undergoing ART treatments and should be considered safe for men's reproductive health.

Evaluation of Female Fertility - AMH and Ovarian Reserve Testing.

Abstract: CONTEXT Evaluation of the infertile female requires an understanding of ovulation and biomarkers of ovarian reserve. Anti-mullerian Hormone (AMH) correlates with growing follicles in a menstrual cycle. Increasingly, AMH has been utilized as a "fertility test". This narrative review describes how to integrate the use of AMH into diagnosis and treatment. EVIDENCE ACQUISITION A PubMed search was conducted to find recent literature on measurements and use of serum AMH as a marker of ovarian reserve and in treatment of infertility. EVIDENCE SYNTHESIS Serum AMH estimates ovarian reserve, helps determine dosing in ovarian stimulation and predicts stimulation response. As such, AMH is a good marker of oocyte quantity but does not reflect oocyte health or chances for pregnancy. Screening of AMH prior to fertility treatment should be utilized to estimate expected response and not to withhold treatment. Low AMH levels may suggest a shortened reproductive window. AMH levels must be interpreted in the context of the endogenous endocrine environment where low FSH, due to hypogonadotropic hypogonadism or hormonal contraceptive usage, may lower AMH without being a true reflection of ovarian reserve. Additionally, there is an inverse correlation between BMI and AMH that does not reflect ovarian response. CONCLUSION AMH is a useful marker of ovarian reserve in reproductive age women. Increased screening of non-infertile women requires a thorough knowledge of situations that may impact AMH levels. In no situation does AMH reflect oocyte health or chances for conception. Age is still the strongest driver in determining success rates with fertility treatments.

The changing tide of human fertility

Abstract: Abstract Over the past half-century, the world has witnessed a steep decline in fertility rates in virtually every country on Earth. This universal decline in fertility is being driven by increasing prosperity largely through the mediation of social factors, the most powerful of which are the education of women and an accompanying shift in life’s purpose away from procreation. In addition, it is clear that environmental and lifestyle factors are also having a profound impact on our reproductive competence particularly in the male where increasing prosperity is associated with a significant rise in the incidence of testicular cancer and a secular decline in semen quality and testosterone levels. On a different timescale, we should also recognize that the increased prosperity associated with the demographic transition greatly reduces the selection pressure on high fertility genes by lowering the rates of infant and childhood mortality. The retention of poor fertility genes within the human population is also being exacerbated by the increased uptake of ART. It is arguable that all of these elements are colluding to drive our species into an infertility trap. If we are to avoid the latter, it will be important to recognize the factors contributing to this phenomenon and adopt the social, political, environmental and lifestyle changes needed to bring this situation under control.

Fertility intentions to have a second or third child under China's three-child policy: a national cross-sectional study.

Abstract: STUDY QUESTION What proportion of people want to have a second or third child after the enactment of the three-child policy in China? SUMMARY ANSWER Under the three-child policy, fertility intention to have a second child was ∼60% (56% of women vs 65% of men), and fertility intention to have a third child was 13% (10% of women vs 17% of men) among the Chinese population. WHAT IS KNOWN ALREADY The Chinese government announced the three-child policy on 31 May 2021, allowing all couples to have up to three children. At present, there is a lack of national surveys on the fertility intentions of women and men to have a second or third child under the three-child policy in China. STUDY DESIGN, SIZE, DURATION In June 2021, a national cross-sectional survey including 9243 respondents aged 18-49 years was conducted online from 31 provinces in China's mainland using a random sampling method. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on the intention to have a second or third child were collected by anonymous questionnaire. Descriptive statistics were performed to assess fertility intentions. Multivariate and multinomial logistic regression analyses were used to assess the association between fertility intentions and the investigated factors. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 60% (5493/9243) of the investigated people (55.6% women vs 64.7% men) intended to have a second child, and 13.0% (1203/9243) of them (10.0% women vs 17.1% men) intended to have a third child under China's three-child policy. For non-child respondents, 46.8% of women and 60.4% of men intended to have a second child. For one-child respondents, 47.8% of women and 53.8% of men intended to have a second child. For two-child respondents, 14.4% of women and 25.9% of men intended to have a third child. The mean desired family size was 1.58 children per woman, which was lower than the 1.76 children per man. Notably, the age-specified fertility intentions of men were always higher than those of women. Women with a college or higher degree (adjusted odds ratio [aOR] 0.60, 95% CI 0.42-0.88) and a high-middle (aOR 0.71, 95% CI 0.53-0.95) or high (aOR 0.64, 95% CI 0.48-0.85) household income, as well as men living in urban areas (aOR 0.71, 95% CI 0.58-0.87) and having a high-middle household income (aOR 0.68, 95% CI 0.52-0.90), were associated with a lower intention to have a third child (all P < 0.05). In contrast, men of public service personnel had a higher intention to have a third child than factory workers (aOR 1.44, 95% CI 1.02-2.04, P < 0.05). Meanwhile, approximately one out of five two-child respondents intended to have a third child, while one out of four two-girl respondents (aOR 2.09, 95% CI 1.44-3.04) were willing to have a third child with a strong preference for boys (12.7% for boys vs 2.7% for girls). Economic and childrearing barriers were the leading barriers to having one more child. LIMITATIONS, REASONS FOR CAUTION The online survey might limit the representativeness of the present study's sample. A large sample size was enrolled and a random sampling method was used to increase the sample diversity and representativeness. WIDER IMPLICATIONS OF THE FINDINGS This study will assist in estimating the impact on population demographic of the three-child policy in China. Multiple efforts are needed to create a fertility-friendly environment for couples, thereby increasing fertility intentions to have one more child and increasing fertility rates. STUDY FUNDING/COMPETING INTEREST(S) No funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Sperm DNA Fragmentation: A Critical Assessment of Clinical Practice Guidelines

Abstract: Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines.

OUP accepted manuscript

Abstract: Abstract STUDY QUESTION What proportion of people want to have a second or third child after the enactment of the three-child policy in China? SUMMARY ANSWER Under the three-child policy, fertility intention to have a second child was ∼60% (56% of women vs 65% of men), and fertility intention to have a third child was 13% (10% of women vs 17% of men) among the Chinese population. WHAT IS KNOWN ALREADY The Chinese government announced the three-child policy on 31 May 2021, allowing all couples to have up to three children. At present, there is a lack of national surveys on the fertility intentions of women and men to have a second or third child under the three-child policy in China. STUDY DESIGN, SIZE, DURATION In June 2021, a national cross-sectional survey including 9243 respondents aged 18–49 years was conducted online from 31 provinces in China’s mainland using a random sampling method. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on the intention to have a second or third child were collected by anonymous questionnaire. Descriptive statistics were performed to assess fertility intentions. Multivariate and multinomial logistic regression analyses were used to assess the association between fertility intentions and the investigated factors. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 60% (5493/9243) of the investigated people (55.6% women vs 64.7% men) intended to have a second child, and 13.0% (1203/9243) of them (10.0% women vs 17.1% men) intended to have a third child under China’s three-child policy. For non-child respondents, 46.8% of women and 60.4% of men intended to have a second child. For one-child respondents, 47.8% of women and 53.8% of men intended to have a second child. For two-child respondents, 14.4% of women and 25.9% of men intended to have a third child. The mean desired family size was 1.58 children per woman, which was lower than the 1.76 children per man. Notably, the age-specified fertility intentions of men were always higher than those of women. Women with a college or higher degree (adjusted odds ratio [aOR] 0.60, 95% CI 0.42–0.88) and a high-middle (aOR 0.71, 95% CI 0.53–0.95) or high (aOR 0.64, 95% CI 0.48–0.85) household income, as well as men living in urban areas (aOR 0.71, 95% CI 0.58–0.87) and having a high-middle household income (aOR 0.68, 95% CI 0.52–0.90), were associated with a lower intention to have a third child (all P &lt; 0.05). In contrast, men of public service personnel had a higher intention to have a third child than factory workers (aOR 1.44, 95% CI 1.02–2.04, P &lt; 0.05). Meanwhile, approximately one out of five two-child respondents intended to have a third child, while one out of four two-girl respondents (aOR 2.09, 95% CI 1.44–3.04) were willing to have a third child with a strong preference for boys (12.7% for boys vs 2.7% for girls). Economic and childrearing barriers were the leading barriers to having one more child. LIMITATIONS, REASONS FOR CAUTION The online survey might limit the representativeness of the present study’s sample. A large sample size was enrolled and a random sampling method was used to increase the sample diversity and representativeness. WIDER IMPLICATIONS OF THE FINDINGS This study will assist in estimating the impact on population demographic of the three-child policy in China. Multiple efforts are needed to create a fertility-friendly environment for couples, thereby increasing fertility intentions to have one more child and increasing fertility rates. STUDY FUNDING/COMPETING INTEREST(S) No funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

OUP accepted manuscript

Abstract: Young adults (YA) diagnosed with rectal cancer are disproportionately impacted by the gonadotoxic effects of treatment and potential subsequent infertility.The purpose of this study was to characterize the prevalence of fertility preservation measures used, reasons why such measures were not used, and correlates of discussion between providers and YA rectal cancer survivors.An online, cross-sectional survey was administered on the Facebook page of a national colorectal cancer (CRC) advocacy organization. Eligible participants were rectal cancer survivors diagnosed before age 50, between 6 and 36 months from diagnosis or relapse, and based in the US.Participants were 148 rectal cancer survivors. Over half of the survivors reported that their doctor did not talk to them about potential therapy-related fertility complications. Only one-fifth of survivors banked sperm (males) or eggs/embryos (females) prior to their cancer therapy. Older age at diagnosis and greater quality of life were significantly associated with a higher likelihood of fertility discussions among males. Greater quality of life was significantly associated with a higher likelihood of fertility discussion among females.These findings indicate that the majority of YA rectal cancer survivors do not receive, or cannot recall, comprehensive cancer care, and help to identify patients with rectal cancer who may be at risk for inadequate fertility counseling. Clinicians should provide proper counseling to mitigate this late effect and to ensure optimal quality of life for YA rectal cancer survivors.

A Review of the Diversity of the Genital Tract Microbiome and Implications for Fertility of Cattle

Abstract: Simple Summary Reproductive systems of cattle contain multiple microbes resident in the female from a young age. Sometimes other harmful microbes can invade the genital tract and cause diseases that impair fertility. Normally, commensal microbes facilitate genital tract homeostasis and produce factors that stimulate male sexual response. For this reason, the type and number of microbes present in the genital tract are important for reproductive tract health, and any disruption of this microbial balance leads to genital diseases. Interestingly, these microbes frequently populate the genital tract of cows, leading to reproductive diseases that perturb fertility. However, a microbiome composed of commensal microbes will likely result in the restoration of uterine health and improved fertility of the cows. Abstract Cattle have a genital microbiome that is established early in life, even before calving. Microbial influx into the reproductive system of cows, during calving or mating, is unavoidable and is likely to alter the commensal microflora composition. It is now well established that a commensal endometrial flora is largely responsible for the overall fertility of cows. These microbes are important for maintenance of structural integrity of the genital mucosal barrier, immunomodulation, and protection against pathogens. Further, the genital microbiome functions in the semiochemical communication between a male and female. An optimal balance between the abundance and diversity of the microbiome is essential to promote female genital tract health. Disruption of this balance leads to dysbiosis and genital diseases and perturbed fertility. As part of the global strategy of One World, One Health, there is a need to reduce antibiotic use in animals. This area of research has the potential to expand the knowledge about the nexus between the endometrial microbiome and fertility including being probiotic in different species.

The health consequences of child marriage: a systematic review of the evidence

Abstract: Child marriage, defined as marriage before 18 years of age, is a violation of human rights and a marker of gender inequality. Growing attention to this issue on the global development agenda also reflects concerns that it may negatively impact health. We conducted a systematic review to synthesize existing research on the consequences of child marriage on health and to assess the risk of bias in this body of literature.We searched databases focused on biomedicine and global health for studies that estimated the effect of marrying before the age of 18 on any physical or mental health outcome or health behaviour. We identified 58 eligible articles, nearly all of which relied on cross-sectional data sources from sub-Saharan Africa or South Asia. The most studied health outcomes were indicators of fertility and fertility control, maternal health care, and intimate partner violence. All studies were at serious to critical risk of bias. Research consistently found that women who marry before the age of 18 begin having children at earlier ages and give birth to a larger number of children when compared to those who marry at 18 or later, but whether these outcomes were desired was not considered. Across studies, women who married as children were also consistently less likely to give birth in health care facilities or with assistance from skilled providers. Studies also uniformly concluded that child marriage increases the likelihood of experiencing physical violence from an intimate partner. However, research in many other domains, including use of contraception, unwanted pregnancy, and sexual violence came to divergent conclusions and challenge some common narratives regarding child marriage.There are many reasons to be concerned about child marriage. However, evidence that child marriage causes the health outcomes described in this review is severely limited. There is more heterogeneity in the results of these studies than is often recognized. For these reasons, greater caution is warranted when discussing the potential impact of child marriage on health. We provide suggestions for avoiding common biases and improving the strength of the evidence on this subject.The protocol of this systematic review was registered with PROSPERO (CRD42020182652) in May 2020.

The environmental and occupational influence of pesticides on male fertility: a systematic review of human studies.

Abstract: BACKGROUND Environment plays a key role in male infertility, changing the incidence in various populations, and pesticides are one of the most studied hazards. The use of the latter has never decreased, jeopardizing the safety of workers and the general population. OBJECTIVE Our purpose was to summarize the results of studies discussing the association between pesticides and male fertility. METHODS A comprehensive literature search was performed through MEDLINE via PubMed, Scopus, and Web of Science. Only human studies were considered. Semen parameters, and DNA integrity were considered to evaluate the effect of pesticides on men. RESULTS A total of 64 studies that investigated their impact in terms of semen parameters (51 studies), chromatin and DNA integrity (25 studies), were included. The most frequently affected parameters were total sperm count sperm motility and morphology, although a reduction in ejaculate volume and concentration occur in several cases. A tangible worsening of semen quality was associated with organochlorines and organophosphates. Furthermore, pesticide exposure, especially pyrethroids, was related to a higher DNA fragmentation index and chromosome aneuploidy in most articles. CONCLUSION The epidemiological evidence supports the association between pesticides and male fertility for workers and the exposed population in terms of semen quality, DNA fragmentation and chromosome aneuploidy. This article is protected by copyright. All rights reserved.

Antioxidants for male subfertility

Abstract: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility.To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men.The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, and two trial registers were searched on 15 February 2021, together with reference checking and contact with experts in the field to identify additional trials.We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included men with idiopathic infertility and normal semen parameters or fertile men attending a fertility clinic because of female partner infertility.We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes.We included 90 studies with a total population of 10,303 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing medically assisted reproduction (MAR). Investigators compared and combined 20 different oral antioxidants. The evidence was of 'low' to 'very low' certainty: the main limitation was that out of the 67 included studies in the meta-analysis only 20 studies reported clinical pregnancy, and of those 12 reported on live birth. The evidence is current up to February 2021. Live birth: antioxidants may lead to increased live birth rates (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.07 to 1.91, P = 0.02, 12 RCTs, 1283 men, I2 = 44%, very low-certainty evidence). Results in the studies contributing to the analysis of live birth rate suggest that if the baseline chance of live birth following placebo or no treatment is assumed to be 16%, the chance following the use of antioxidants is estimated to be between 17% and 27%. However, this result was based on only 246 live births from 1283 couples in 12 small or medium-sized studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.22, 95% CI 0.85 to 1.75, 827 men, 8 RCTs, P = 0.27, I2 = 32%). Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, P < 0.00001, 20 RCTs, 1706 men, I2 = 3%, low-certainty evidence) compared with placebo or no treatment. This suggests that, in the studies contributing to the analysis of clinical pregnancy, if the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 15%, the chance following the use of antioxidants is estimated to be between 20% and 30%. This result was based on 327 clinical pregnancies from 1706 couples in 20 small studies. Adverse events Miscarriage: only six studies reported on this outcome and the event rate was very low. No evidence of a difference in miscarriage rate was found between the antioxidant and placebo or no treatment group (OR 1.46, 95% CI 0.75 to 2.83, P = 0.27, 6 RCTs, 664 men, I2 = 35%, very low-certainty evidence). The findings suggest that in a population of subfertile couples, with male factor infertility, with an expected miscarriage rate of 5%, the risk of miscarriage following the use of an antioxidant would be between 4% and 13%. Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal discomfort when compared with placebo or no treatment (OR 2.70, 95% CI 1.46 to 4.99, P = 0.002, 16 RCTs, 1355 men, I2 = 40%, low-certainty evidence). This suggests that if the chance of gastrointestinal discomfort following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 7%. However, this result was based on a low event rate of 46 out of 1355 men in 16 small or medium-sized studies, and the certainty of the evidence was rated low and heterogeneity was high. We were unable to draw conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions.In this review, there is very low-certainty evidence from 12 small or medium-sized randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-certainty evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal discomfort, based on very low-certainty evidence. Subfertile couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials studying infertile men and reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.