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An important drawback of anticancer chemotherapy is the harm it causes to healthy cells. Cyclophosphamide (CP) is a widely used chemotherapeutic alkylating agent that is regularly used in cancer treatment. However, it can cause severe side effects, including genotoxicity, due to its ability to damage DNA. This toxicity is thought to be associated with oxidative stress induced by an excessive amount of reactive oxygen species (ROS). Therefore, there is a specific focus on the potential effects of anticancer treatments on fertility. Due to the increasing life expectancy of cancer patients, those desiring parenthood may face the negative impacts of therapies. Utilizing substances with antioxidant and cytoprotective characteristics to protect the reproductive system from harmful consequences during chemotherapy would be highly beneficial. This review introduces the physiological and pathological roles of ROS in the reproductive systems of both males and females, then we address the adverse effects of CP administration on infertility and discuss how antioxidants can reverse these effects., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Increasing awareness of gonadotoxicity in cancer treatments and infertility risk is essential for counseling young cancer patients. While fertility preservation options are available in many countries, limited data on gonadotoxicity hinder recommendations, especially for soft tissue cancers. This review, part of the FertiTOX project (www.fertitox.com), organized by FertiPROTEKT (www.fertiprotekt.com), aims to address this knowledge gap to improve fertility preservation guidance. We performed a systematic literature search on gonadotoxicity in soft tissue sarcoma (STS) cancer treatments. Only patients without metastases or recurrent disease were considered. "Suspected infertility" was defined based on low ovarian reserve parameters, low inhibin B levels, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia due to limited infertility data. The study quality was assessed using the Newcastle-Ottawa Scale. The search yielded 3309 abstracts, with 138 undergoing full-text analysis. Eight studies on STS were included. Suspected infertility was observed in 20 of 28 females (71.4%, range 0-100%) and 38 of 63 males (60.3%, range 34.8-100%) with STS. Six of the eight studies received high-quality scores on the NOS, while two received a fair score. Our data suggest a high risk of infertility from chemotherapy in pre- and postpubertal STS survivors. This underscores the importance of considering fertility preservation measures when counseling these patients.

Environmental chemical exposure has been rising over the past few decades but its impact on fertility remains uncertain. We assessed exposures to 23 common chemicals across a range of sociodemographic characteristics and their relationship with self-reported infertility. The analytic sample was non-pregnant women aged 18-49 years without a history of hysterectomy or oophorectomy (n = 2579) from the National Health and Nutrition Examination Survey (2013-2016). Environmental chemical exposure was assessed with biospecimens and dichotomized as high and low levels of exposure based on the median. Logistic regression models estimated the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for the association between high levels of exposure and infertility, adjusted for age, race, education level, family income, and smoking status. We observed associations between infertility and cadmium [aOR: 1.88; 95% CI: 1.02-3.47] and arsenic [aOR: 1.88 (1.05-3.36)]. Two pesticides hexachlorobenzene [OR: 2.04 (1.05-3.98)] and oxychlordane [OR: 2.04 (1.12-3.69)] were also associated with infertility in unadjusted analyses. There were negative associations with two Per- and polyfluoroalkyl substances with n-perfluorooctanoic acid [aOR: 0.51: (0.30-0.86)] and n-perfluorooctane sulfonic acid [aOR: 0.51: (0.26-0.97). Specific chemicals may contribute to infertility risk, highlighting the need for targeted public health strategies to mitigate exposure.

It is important to understand the impact of consumer chemical exposure and fecundity, a couple's measure of probability of successful conception, given approximately 15% of couples experience infertility. Prior research has generally found null associations between bisphenol and phthalate exposure and fecundability, measured via time to pregnancy (TTP). However, this research has not been updated with current chemical exposures and have often lacked diversity in their study populations. We evaluated the associations between common bisphenol and phthalate chemical exposure groups and TTP as well as subfecundity (TTP>12 months) in the New York University Children's Health Study, a diverse pregnancy cohort from 2016 onward. Using first-trimester spot-urine samples to measure chemical exposure and self-reported TTP from first-trimester questionnaires, we observed a significant adverse association between total bisphenol exposure and certain phthalate groups on TTP and odds of subfecundity. Furthermore, in a mixtures analysis to explore the joint effects of the chemical groups on the outcomes, we found evidence of a potential interaction between total bisphenol exposure and low-molecular weight phthalates on TTP. Future research should continue to update our knowledge regarding the complex and potentially interacting effects of these chemicals on reproductive health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mia Charifson reports financial support was provided by National Science Foundation. Mengling Liu reports financial support was provided by National Institute of Environmental Health Sciences. Eunsil Seok reports financial support was provided by National Institute of Environmental Health Sciences. Yuyan Wang reports financial support was provided by National Institute of Environmental Health Sciences. Leonardo Trasande reports financial support was provided by National Institutes of HealthOffice of the Director. Linda Kahn reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Declining total fertility rates have been observed in low- and middle-income countries (LMICs). However, it remains unclear if this trend is related to a reduction in fecundity of general population. Research evidence on contributing factors to fecundity reduction is also limited. We aimed to first estimate couple fecundity in LMICs and then investigate its association with ambient particulate matter (PM) exposure., Methods: Using the information from Demographic and Health Surveys between 2003 and 2019, we estimated median time to pregnancy (TTP) and infertility prevalence across 30 LMICs, by employing a current duration approach. Individual PM (PM 1 , PM 2.5 , and PM 10 ) exposure during the period of 'at risk' of pregnancy was assessed by months. An accelerated failure model was used to elucidate the association between monthly time-varying PM exposure and TTP. Subsequently, we estimated the prolonged TTP attributable to PM exposures above the World Health Organization (WHO)'s recommended air quality level in 2021., Results: Within the study regions, median TTP ranged from 6.90 (95 % CI 6.02-7.87) months in Latin America & Caribbean to 10.29 (95 % CI 9.28-11.36) months in East Asia & Pacific, with corresponding infertility prevalence varying from 33 % (95 % CI 29 %-36 %) to 44 % (95 % CI 41 %-48 %). Our estimations indicated that TTP was 1.08 (95 % CI: 0.99-1.18), 1.12 (95 % CI 1.06-1.19), and 1.05 (95 % CI 1.03-1.07) times longer for every 10 μg/m 3 increment in PM 1 , PM 2.5 , and PM 10 , respectively. The prolonged TTP attributable to PM exposures surpassing the WHO guideline ranged from 0.11 to 2.81 months across the studied regions., Discussion: Ambient particulate matter is identified as a potential contributing factor to impaired fecundity in general population of LMICs. The findings underscore the importance of coordinated efforts to control ambient air pollution to mitigate the risk of fecundity reduction among the general population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aims to describe patterns of beliefs about contraceptive-induced infertility and assess their relationship with current contraceptive use, including whether these relationships vary by parity and residence., Design: We use data from Performance Monitoring for Action Ethiopia, a nationally representative, cross-sectional survey of 7491 women, aged 15-49, to assess agreement with the statement 'If I use family planning, I may have trouble getting pregnant next time I want to.' We used multilevel hierarchical models to identify the association between agreement and use of a hormonal method of contraception among 3882 sexually active, fecund women who wish to prevent pregnancy. We include interaction terms for parity and residence., Results: 4 in 10 women disagreed (42.3%) and 2 in 10 strongly disagreed (20.7%) with the statement. Relative to women who strongly disagreed, women who disagreed and women who agreed had significantly lower odds of using a hormonal method of contraception (adjusted OR (aOR) 0.65, 95% CI 0.44 to 0.97 and 0.46, 95% CI 0.46, 95% CI 0.30 to 0.70). The effect of agreeing with the statement was strongest among high parity women (aOR 0.54, 95% CI 0.30 to 0.95). Greater agreement with the statement at the community-level use was associated with a reduction in the odds of using hormonal contraception but only among rural women., Conclusions: Efforts to address concerns around contraceptive-induced fertility impairment through the provision of comprehensive counselling and through community education or mass media campaigns are necessary, particularly among high-parity women and in rural communities. Interventions should acknowledge the possibility of delayed return to fertility for specific methods and attempt to address the root causes of concerns., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Across the globe, many species of insects are facing population decline. This is largely driven by anthropogenic changes to the environment, including the widespread exposure of invertebrates to endocrine disrupting chemicals (EDCs), which impair fertility. To test whether generations of Drosophila melanogaster born from parents exposed to a common dietary EDC, equol, could recover reproductive function, we quantified the reproductive capacity of the two subsequent generations. Using a novel suite of flow cytometry assays to assess sperm functionality in real time, we find that sperm function is compromised across three generations, even after non-exposed in individuals contribute to the breeding population. Though the sex ratio alters in response to EDC exposure, favouring the survival of female offspring, most lineages with ancestral EDC exposure exhibit persistent subfertility in both the male and female. Male offspring with ancestral EDC exposure present with reduced fertility and dysfunctional spermatozoa, whereby spermatozoa are metabolically stressed, lack DNA integrity and present with permanent epigenetic alterations. Across generations, male and female offspring demonstrate distinct patterns of reproductive characteristics, depending upon the specific lineage of EDC exposure. Our results illustrate how dietary EDCs present in agricultural plants could promote transgenerational subfertility and contribute to declining insect populations., (© 2024. The Author(s).)

Human fertility is impacted by changes in lifestyle and environmental deterioration. To increase human fertility, assisted reproductive technology (ART) has been extensively used around the globe. As early as 2009, the Endocrine Society released its first scientific statement on the potential adverse effects of environmental endocrine-disrupting chemicals (EDCs) on human health and disease development. Chemicals known as phthalates, frequently employed as plasticizers and additives, are common EDCs. Numerous studies have shown that phthalate metabolites in vivo exert estrogen-like or anti-androgenic effects in both humans and animals. They are associated with the progression of a range of diseases, most notably interference with the reproductive process, damage to the placenta, and the initiation of chronic diseases in adulthood. Phthalates are ingested by infertile couples in a variety of ways, including household products, diet, medical treatment, etc. Exposure to phthalates may exacerbate their infertility or poor ART outcomes, however, the available data on phthalate exposure and ART pregnancy outcomes are sparse and contradictory. Therefore, this review conducted a systematic evaluation of 16 papers related to phthalate exposure and ART pregnancy outcomes, to provide more aggregated results, and deepen our understanding of reproductive outcomes in infertile populations with phthalate exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Organophosphate pesticides such as malathion are the most widely used pesticides. Despite endocrine-disrupting effects, there is a paucity of information regarding chronic exposure to non-persistent organopesticides such as malathion. The purpose of this study is to describe the exposure burden among U.S. residents as well as possible impacts on fertility., Methods: Population-based data collected by the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2016 were used to perform a retrospective analysis on urinary concentrations of malathion diacid. Samples were assessed from 1703 adult participants, statistically weighted to represent over 231 million individuals. General linear models were used to examine associations between exposure and reproductive health measures among pre-menopausal women., Results: Detectable concentrations of malathion diacid were identified in 16.1 % (n = 254) of samples. Concentrations were higher among women who reported seeing a physician due to difficulties becoming pregnant (P < 0.001; r 2  = 0.12) as well as among women who reported trying for at least a year to become pregnant (P < 0.001; r 2  = 0.06)., Conclusions: Exposure to malathion is associated with a history of reproductive health challenges among women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Exposure to ambient fine particulate matter (PM 2.5 ) has been associated with reduced human fecundity. However, the attributable burden has not been estimated for low- and middle-income countries (LMICs), where the exposure-response function between PM 2.5 and the infertility rate has been insufficiently studied., Objective: This study examined the associations between long-term exposure to PM 2.5 and human fecundity indicators, namely the expected time to pregnancy (TTP) and 12-month infertility rate (IR), and then estimated PM 2.5 -attributable burden of infertility in LMICs., Methods: We analyzed 164,593 eligible women from 100 Demographic and Health Surveys conducted in 49 LMICs between 1999 and 2021. We assessed PM 2.5 exposures during the 12 months before a pregnancy attempt using the global satellite-derived PM 2.5 estimates produced by Atmospheric Composition Analysis Group (ACAG). First, we created a series of pseudo-populations with balanced covariates, given different levels of PM 2.5 exposure, using a matching approach based on the generalized propensity score. For each pseudo-population, we used 2-stage generalized Gamma models to derive TTP or IR from the probability distribution of the questionnaire-based duration time for the pregnancy attempt before the interview. Second, we used spline regressions to generate nonlinear PM 2.5 exposure-response functions for each of the two fecundity indicators. Finally, we applied the exposure-response functions to estimate number of infertile couples attributable to PM 2.5 exposure in 118 LMICs., Results: Based on the Gamma models, each 10 µg/m 3 increment in PM 2.5 exposure was associated with a TTP increase by 1.7 % (95 % confidence interval [CI]: -2.3 %-6.0 %) and an IR increase by 2.3 % (95 %CI: 0.6 %-3.9 %). The nonlinear exposure-response function suggested a robust effect of an increased IR for high-concentration PM 2.5 exposure (>75 µg/m 3 ). Based on the PM 2.5 -IR function, across the 118 LMICs, the number of infertile couples attributable to PM 2.5 exposure exceeding 35 µg/m 3 (the first-stage interim target recommended by the World Health Organization global air quality guidelines) was 0.66 million (95 %CI: 0.061-1.43), accounting for 2.25 % (95 %CI: 0.20 %-4.84 %) of all couples affected by infertility. Among the 0.66 million, 66.5 % were within the top 10 % high-exposure infertile couples, mainly from South Asia, East Asia, and West Africa., Conclusion: PM 2.5 contributes significantly to human infertility in places with high levels of air pollution. PM 2.5 -pollution control is imperative to protect human fecundity in LMICs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Phthalates (PAEs) are endocrine-disrupting chemicals ubiquitously found in the environment. This study aimed to examine the association between exposure of PAEs and subfecundity in preconception couples., Methods: This is a nested case-control study based on preconception cohort. Preconception couples with intention to conceive were enrolled and followed up until a clinically confirmed pregnancy or 12 menstrual cycles of preparation for conception. A total of 107 couples with subfecundity- time to pregnancy (TTP) more than 12 menstrual cycles, and 144 couples ≤12 cycles were included in the analysis. The levels of PAE metabolites in one spot urine samples were detected and compared between the groups. The weighted quantile sum (WQS) regression model and Bayesian kernel machine regression (BKMR) model were used to examine the joint effects of couples' exposure to PAEs on subfecundity., Results: Using the multivariate binary logistic regression model, compared to the lowest quartile of urinary ∑PAEs concentration group, both preconception females (aOR=2.42, 95% CI: 1.10-5.30, p=0.027) and males (aOR=2.99, 95% CI: 1.36-6.58, p=0.006) in the highest quartile group had an increased risk of subfecundity, and a dose-response relationship was observed between PAEs and the risk of subfecundity. The WQS analyses found that co-exposure to PAE mixture was a risk factor for subfecundity in preconception female (aOR=1.76, 95% CI: 1.38-2.26, p<0.001), male (aOR=1.58, 95% CI: 1.20-2.08, p=0.001), and couple (aOR=2.39, 95% CI: 1.61-3.52, p<0.001). The BKMR model found a positive combined effect of mixed exposure to PAEs on the risk of subfecundity., Conclusions: PAEs increase the risk of subfecundity in preconception couples. Our research reinforced the need of monitoring PAE exposure for the purpose of improving human reproductive health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs., Methods: In this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility., Results: PCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea., Conclusion: The findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea., 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 © 2023 Zhao, Wang, Song, Han, Wang, Zhao, Zhang and Zhang.)

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Children's Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000-2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction: There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy., Objectives: Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women., Materials and Methods: Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group., Results: We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension., Conclusion: Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations., (Copyright © 2023 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Clinical studies on the relationship between pesticide exposure at home and infertility in the general population are scarce. Whether the antioxidant nutrients or other health-related factors affect the pesticide-infertility relationship remains unknown. This nationwide study screened 29,400 participants of the National Health and Nutrition Examination Surveys conducted between 2013 and 2018. The participants were subdivided according to dietary zinc intake based on the recommended dietary allowances as the low-zinc and high-zinc groups (< 8 and ≥ 8 mg/day, respectively), and according to body mass index (BMI; cut-off 28 kg/m 2 ) as the low-BMI and high-BMI groups. Participants who were exposed to pesticides at home had an increased risk of infertility (odds ratio [OR] = 1.56, 95% confidence intervals [CI]: 1.06-2.29). The incidence of infertility differed in low-zinc and high-zinc groups (OR, 95% CI: 2.38, 1.40-4.06 vs. 0.98, 0.53-1.79, respectively), indicating an interaction between pesticide exposure and zinc intake in households (P = 0.047), which suggests that a zinc-rich diet may reduce the risk of pesticide-induced infertility. Similarly, the relationship between pesticide exposure and infertility risk differed in the low-BMI and high-BMI groups (OR, 95% CI: 0.90, 0.42-1.93 vs. 2.23, 1.39-3.58, respectively; P = 0.045), suggesting that high BMI may intensify the infertility risk caused by pesticide exposure. These new findings reveal the antagonistic and synergistic effect of zinc and obesity, respectively, in pesticide-induced infertility risk and suggest that individuals who are obese and on a low-zinc diet may be more susceptible to infertility induced by household pesticide exposure., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: COVID-19 has had a catastrophic impact on the world. The current death toll far exceeds 6 million and large numbers of patients are experiencing long-term medical and psychiatric morbidity from the infection. The immunopathology of severe COVID-19 is now better understood. In severely affected patients, there is a chaotic, destructive immune response triggered by SARS-CoV-2, where autoimmunity features prominently., Areas Covered: COVID-19 vaccines ensure a coordinated, balanced immune response to future SARS-CoV-2 infection. The rapid global deployment of effective COVID-19 vaccines has been hindered by financial, logistical and political barriers. Of concern is increasing vaccine hesitancy caused by unfounded conspiracy theories of vaccine adverse effects, often fueled by misinformation and disinformation on social media., Expert Opinion: This perspective discusses the potential impact of the so-called Autoimmune/autoinflammatory Syndrome Induced by Adjuvants (ASIA) on COVID-19 vaccine uptake. Proponents of the ASIA syndrome have inappropriately linked infertility to HPV vaccines and have recently suggested antigenic cross-reactivity between SARS-CoV-2 and ovarian follicles. COVID-19 vaccines have also been linked to ASIA and unfounded fear of infertility is a leading cause of vaccine hesitancy. Vaccine hesitancy caused by spurious disorders such as ASIA are likely to harm individuals and delay global vaccination efforts leading to emergence of vaccine and monoclonal antibody-resistant SARS-CoV-2 variants, thereby prolonging the COVID-19 pandemic.

Untainted environment promotes health, but the last few decades experienced steep upsurge in environmental contaminants posing detrimental physiological impact. The responsible factors mainly include the exponential growth of human population, havoc rise in industrialization, poorly planned urbanization, and slapdash environment management. Environmental degradation can increase the likelihood of human exposure to heavy metals, resulting in health consequences such as reproductive problems. As a result, research into metal-induced causes of reproductive impairment at the genetic, epigenetic, and biochemical levels must be strengthened further. These metals impact upon the female reproduction at all strata of its regulation and functions, be it development, maturation, or endocrine functions, and are linked to an increase in the causes of infertility in women. Chronic exposures to the heavy metals may lead to breast cancer, endometriosis, endometrial cancer, menstrual disorders, and spontaneous abortions, as well as pre-term deliveries, stillbirths. For example, endometriosis, endometrial cancer, and spontaneous abortions are all caused by the metalloestrogen cadmium (Cd); lead (Pb) levels over a certain threshold can cause spontaneous abortion and have a teratogenic impact; toxic amounts of mercury (Hg) have an influence on the menstrual cycle, which can lead to infertility. Impact of environmental exposure to heavy metals on female fertility is therefore a well-known fact. Thus, the underlying mechanisms must be explained and periodically updated, given the growing evidence on the influence of increasing environmental heavy metal load on female fertility. The purpose of this review is to give a concise overview of how heavy metal affects female reproductive health., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective., Methods: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups., Results: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use., Conclusion: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective., Clinical Trials: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 ., (© 2022. The Author(s).)

In order to analyze and examine the TVCDS images of infertile patients, this paper conducted an in-depth study based on the symptoms of polycystic ovary syndrome. Through the sample size estimation method, mathematical analysis, and other methods, the image examination of the polycystic ovary in TVCDS was successfully analyzed. 86 cases of infertile patients with PCS were divided into a control group treated with clomiphene alone and an observation group treated with clomiphene combined with TCM periodic therapy, with 43 patients in each group. The therapeutic effects of the two groups were compared and analyzed. Results show that the treatment effective rate and pregnancy success rate of the observation group were 95.35% and 88.37%, respectively, and those of the control group were 83.72% and 76.74%, respectively. The difference between the two groups was statistically significant ( P < 0.05). It was understood that the main pathogenesis of polycystic ovary syndrome is the abnormal balance of kidney, qi , and blood meridians. Thus, the balance of kidney-anemone-chong Ren-uprisal is broken and the result is infertility symptoms or irregular menstruation. After a study on TVCDS in infertile patients, it was observed that the levels of progesterone (P) and luteinizing hormone (LH) in patients with irregular menstruation were significantly increased. The increase was higher than that in the control group, with an overall negative rate of 4.00%, compared with 18.00% of the control group, showing a significant difference. It also indicates that TVCDS image examination has a very significant effect on improving menstrual irregularities and reducing the incidence of adverse reactions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hongju Duan et al.)

Nirmatrelvir (PF-07321332; NMV) the antiviral component of PAXLOVID™ is a potent and selective inhibitor of the SARS-CoV-2 main protease (M pro ), which plays a critical role in viral replication. PAXLOVID, comprised of nirmatrelvir and ritonavir (used as a pharmacokinetic enhancer), is an oral therapy currently in development as a therapeutic option for those infected with SARS-CoV-2 to prevent progression to severe disease, hospitalization, and death. PAXLOVID has been shown to be efficacious against hospitalization and death in two Phase 2/3 clinical studies that evaluated non hospitalized patients both with and without high risk factors for progression to severe illness. Given that males and females of reproductive age are included in the intended patient population, we assessed the potential effects of NMV up to the limit dose of 1000 mg/kg/day in ICH guideline embryo-fetal development studies in rats and rabbits, and a fertility and early embryonic development study in rats. There were no effects on male and female fertility or early embryonic development in rats, and no severe manifestations of developmental toxicity in rats or rabbits. The lack of adverse findings reported here in nonclinical species is consistent with the intended therapeutic target of NMV (a virus specific protein not present in mammalian cells), the favorable off-target selectivity profile, and lack of genetic toxicity. The results of these nonclinical studies with NMV along with existing ritonavir safety information indicate that there are no clinically relevant risks associated with PAXLOVID administration during pregnancy and in males and females of reproductive age., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In continuation of the search for new anthelmintic natural products, the study at hand investigated the nematicidal effects of the two naturally occurring quassinoids ailanthone and bruceine A against the reproductive system of the model nematode Caenorhabditis elegans to pinpoint their anthelmintic mode of action by the application of various microscopic techniques. Differential Interference Contrast (DIC) and the epifluorescence microscopy experiments used in the presented study indicated the genotoxic effects of the tested quassinoids (c ailanthone = 50 µM, c bruceine A = 100 µM) against the nuclei of the investigated gonadal and spermathecal tissues, leaving other morphological key features such as enterocytes or body wall muscle cells unimpaired. In order to gain nanoscopic insight into the morphology of the gonads as well as the considerably smaller spermathecae of C. elegans , an innovative protocol of polyethylene glycol embedding, ultra-sectioning, acridine orange staining, tissue identification by epifluorescence, and subsequent AFM-based ultrastructural data acquisition was applied. This sequence allowed the facile and fast assessment of the impact of quassinoid treatment not only on the gonadal but also on the considerably smaller spermathecal tissues of C. elegans . These first-time ultrastructural investigations on C. elegans gonads and spermathecae by AFM led to the identification of specific quassinoid-induced alterations to the nuclei of the reproductive tissues (e.g., highly condensed chromatin, impaired nuclear membrane morphology, as well as altered nucleolus morphology), altogether implying an apoptosis-like effect of ailanthone and bruceine A on the reproductive tissues of C. elegans .

Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations., 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 Zatecka, Bohuslavova, Valaskova, Margaryan, Elzeinova, Kubatova, Hylmarova, Peknicova and Pavlinkova.)

Genotoxicity has been identified as the main cause of infertility and a variety of cancers. The mechanisms affect the structure, quality of the information or the segregation of DNA and are not inherently correlated with mutagenicity. The concept of genotoxicity, the chemical classes that cause genetic damage and the associated mechanisms of action are discussed here. Hazardous effects of pharmaceuticals, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials are, in large part, identified by genotoxicity and mutagenicity tests. These are critical and early steps in industrial and regulatory health assessment. Though several in vitro experiments are commonly used and approval by regulatory agencies for commercial licensing of drugs, their accuracy in human predictions for genotoxic and mutagenic effects is frequently questioned. Treatment of real and functional genetic toxicity problems depends in detail on the knowledge of mechanisms of DNA damage in the molecular, subcellular, cellular and tissue or organ system levels. Current strategies for risk assessment of human health need revisions to achieve robust and reliable results for optimizing their effectiveness. Additionally, computerized methods, neo-biomarkers leveraging '-omics' approaches, all of which can provide a convincing genotoxicity evaluation to reduce infertility and cancer risk., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This comment piece explores the decision in Whittington Hospital NHS Trust v XX [2020] UKSC 14. It argues that despite notable shifts in public policy in respect of the acceptability of surrogacy as a means of family formation in the past twenty years, the Supreme Court has taken a step too far in deciding that foreign commercial surrogacy is as widely socially accepted. This impacts on the reasonableness of any claim for damages in negligence for the costs of commercial surrogacy. It is posited that the issue of whether damages for foreign commercial surrogacy are reasonable or not will be the key battleground in future negligence cases of this type., (© The Author(s) 2020. Published by Oxford University Press; All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The reproductive performance of most of the species is adversely affected by hazardous heavy metals like lead, cadmium, mercury, arsenic, zinc, and copper. Heavy metals are liberated in the environment by natural sources like rock weathering, volcanic eruption, and other human activities like industrial discharge, mineral mining, automobile exhaust, and so forth. Heavy metals alter several reproductive functions in both males and females like a decrease in sperm count, motility, viability, spermatogenesis, hormonal imbalance, follicular atresia, and delay in oocyte maturation, and so forth, and thus, forms an important aspect of reproductive toxicology. The present review compiles toxicity aspects of various heavy metals and their efficacy and mechanism of action in mammals., (© 2021 Wiley Periodicals LLC.)

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.

Phthalates are pervasive compounds, and due to the ubiquitous usage of phthalates, humans or even children are widely exposed to them. Since phthalates are not chemically bound to the plastic matrix, they can easily leach out to contaminate the peripheral environment. Various animal and human studies have raised vital health concern including developmental and reproductive toxicity of phthalate exposure. The present review is based upon the available literature on phthalates with respect to their reproductive toxic potential. Common reproductive effects such as declined fertility, reduced testis weight, variations in accessory sex organs and several female reproductive disorders appeared to be largely associated with the transitional phthalates. Among the higher molecular weight phthalates (≥ C7), di-isononyl phthalate (DINP) produces some minor effects on development of male reproductive tract and among low molecular weight phthalates (≤C3), di-methyl (DMP) and di-isobutyl (DIBP) phthalate produce some adverse effects on male reproductive system. Whereas transitional phthalates such as di-butyl phthalate, benzyl butyl phthalate, and di-(2-ethylhexyl) phthalate have shown adverse effects on female reproductive system. Owing to these, non-toxic alternatives to phthalates may be developed and use of phthalates could be rationalized as an important issue where human reproduction system is involved. Though, more epidemiological studies are needed to substantiate the reported findings on phthalates., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Despite a significant amount of data on incidence and therapy of immune-related adverse events affecting virtually all organ systems, the potential impact of immune checkpoint inhibitors (ICIs) on gonadal function has not been sufficiently studied. The limited evidence available suggests that ICI-related primary hypogonadism due to orchitis as well as secondary hypogonadism due to hypophysitis are a potential risk for infertility. A systematic investigation of gonadal function under ICIs is warranted given the increasing application of ICIs in the adjuvant setting, among young adults and children and the possible influence of sex hormone levels on the efficacy and toxicity of ICIs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is well established that cancer and its treatment, whether by chemotherapy, radiotherapy, hormone therapy, or surgery, can adversely impact reproductive function in both women and men. The effects of cancer treatment on reproductive function in both sexes may lead to loss of fertility, sexual desire and function, and hormone deficiency, which results in additional long-term morbidity in more than a third of patients. Given the importance of reproductive function to most people, and the often devastating effect of cancer treatment on it, we propose that proactive assessment of the functional and endocrinological impact of treatment be made a vital component of the assessment of modern cancer treatment, and should be a routine part of discussions with patients before and after treatment, both in trials and in routine care. Reproductive counselling should be proactive and encouraged, as implementation of such counselling has been shown to be beneficial to patient mental health, quality of life, and adherence to treatment. Similarly, efforts should be made to provide more adequate and accurate information to patients, as well as to offer appropriate fertility preservation approaches, which may potentially influence their treatment decisions., Competing Interests: Conflict of interest statement D.C. reports no financial competing interests. D.C. reports participating in an advisory board for, and acting as a consultant for, Roche Diagnostics. Both positions involved reimbursement to his employer. FC. reports receiving honoraria from AstraZeneca, BMS, Lilly, Merck and Roche Diagnostics, and his institution receiving research funding from Roche Diagnostics and AstraZeneca. F.P. reports receiving honoraria in the last three years from AstraZeneca, Ipsen and Roche Diagnostics. I.D. reports acting as a consultant for Roche Diagnostics, and receiving speaker honoraria from Novartis. I.D. reports receiving support for congress participation from Ferring and Theramex. M.L. reports acting as a consultant for Novartis, Roche and AstraZeneca, and receiving honoraria from Theramex, Roche, Novartis, Pfizer, Takeda and Lilly. R.A.A. reports acting as a consultant for Roche Diagnostics, IBSA, Merck, Ferring, NeRRE Therapeutics and Sojournix Inc. S.M.N. reports participating in advisory boards and receiving speaker or consultancy fees from Access Fertility, Beckman Coulter, Ferring, Finox, Merck, MSD, Roche Diagnostics and The Fertility Partnership. S.M.N. reports receiving grant funding from government, charity and industry funders, including Roche Diagnostics and Ferring Pharmaceuticals. A.M. reports no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Through our daily diet, we are exposed to a variety of food contaminants. Yet, assessing the cumulative health risk of chemical mixtures remains a challenge. Using a recently developed method, the modified Reference Point Index (mRPI), the cumulative risks posed by contaminant mixtures were assessed for their effects on reproduction and development. Since these effects can be quite diverse, a tiered approach was adopted to elucidate the risks at a more detailed level based on specific toxicological endpoints. An additional analysis was performed using the modified Maximum Cumulative Ratio (mMCR), which provides the determination of risk-dominating substances in the mixture. Our method represents a novel useful tool to screen and prioritise contaminant mixtures regarding their potential health risks. We found, that in the majority of the calculated scenarios a single substance dominates the cumulative risks. Lead was found to be the primary factor for adverse effects on reproduction and neuronal development of children. Perchlorate was identified as the most prominent risk factor for child development in generalCumulative risks of trichothecenes were dominated by deoxynivalenol. Concerning the impact on pre- and neonatal development, the co-exposure of several substances resulted in increased risks, with none of the considered contaminants dominating substantially., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: CYC remains an important treatment option for Behçet's syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients., Methods: We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome., Results: Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15-26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients., Conclusion: Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Primary ovarian insufficiency is a cause of infertility that affects about 1% of women under 40 years old, and is considered as idiopathic in 75% of cases. This review aims to carry out a critical synthesis of the knowledge of the chemical agents likely to affect follicular stock in humans and / or animals, by direct toxicity to follicles, or by increasing their recruitments. For the majority of toxic agents, only experimental data are currently available. We propose a strategy to encourage progress in identifying occupational factors responsible for premature ovarian failure.

We aimed to explore the possible neurotoxicity and infertility mechanisms of prolonged metronidazole (MTZ) use and the effects of antioxidant grapefruit (GP) co-therapy on MTZ-induced complications. Sixty male albino Wistar rats were divided into four groups ( n = 15 each). Group I (control group) received 1% dimethyl sulfoxide (27 ml/ kg/day), group II (MTZ group) received MTZ (400 mg/kg/day), group III (MTZ + GP) received MTZ (400 mg/kg/ day) plus GP juice (27 ml/kg/ day) and group IV (GP group) received GP juice (27 ml/kg) for 60 days. Semen analyses were performed. Free testosterone, gonadotrophin (follicle-stimulating hormone (FSH) and luteinizing hormone) and thiamine levels were measured. Samples of cerebellar, testicular and epididymal tissues were used for both colorimetric assays of oxidative stress markers and histopathological examinations. Significant decreases in the sperm count, percent total sperm motility, serum thiamine levels, free testosterone levels and FSH levels were observed in the MTZ and MTZ + GP groups ( p < 0.05 for all parameters). Significantly higher oxidative stress levels ( p < 0.05) were observed in the cerebellar and testicular tissue homogenates of these groups than in those of the control group, and associated disruptions in the cerebellar, testicular and epididymal structures were apparent compared to those of the control group. Although the GP group showed a significantly higher sperm count and significantly lower oxidative stress than the control group ( p < 0.05), with histological similarity to the control group, the GP group exhibited significantly higher prolactin levels and lower free testosterone and FSH levels than the control group ( p < 0.05). Oxidative stress and decreased thiamine levels could explain the MTZ-induced neurotoxicity and infertility side effects that aggravated by GP co-administration.

Opioids are pivotal therapeutics in the management of escalated chronic pain (moderate-severe). In the last two decades, the increased prescription rate and the prolonged usage of opioids shed light on opioid-induced endocrinopathy. Opioid-induced hypogonadism (OHG) results upon long-term opioid therapy. Clinically, patients with OHG are presented mainly by sexual dysfunction and infertility. Opioid clinical use in pain therapy is indispensable. However, the resultant sexual endocrinopathy cannot be overlooked and hence hormonal replacement therapy with regular monitoring of the patients represents a potential therapeutic strategy while avoiding opioids in patients with guaranteed long therapeutic exposure and switching to using low-dose naltrexone as alternative represents a possible prophylactic measure to ensure therapeutic compliance and secure a good life quality of patients., (© 2019 John Wiley & Sons Australia, Ltd.)

Finasteride is a 5α-reductase enzyme inhibitor that has been approved for the treatment of male androgenic alopecia since 1997. Over time, it has been considered a safe and well-tolerated drug with rare and reversible side effects. Recently there have been reports of adverse drug-related reactions that persisted for at least three months after discontinuation of this drug, and the term post-finasteride syndrome arose. It includes persistent sexual, neuropsychiatric, and physical symptoms. Studies to date cannot refute or confirm this syndrome as a nosological entity. If it actually exists, it seems to occur in susceptible people, even if exposed to small doses and for short periods, and symptoms may persist for long periods. Based on currently available data, the use of 5α-reductase inhibitors in patients with a history of depression, sexual dysfunction, or infertility should be carefully and individually assessed., (Copyright © 2020. Published by Elsevier España, S.L.U.)

Insecticides, a heterogeneous group of chemicals, are widely used in agriculture and household practices to avoid insect-inflicted damage. Extensive use of insecticides has contributed substantially to agricultural production and the prevention of deadly diseases by destroying their vectors. On the contrary, many of the insecticides are associated with several adverse health effects like neurological and psychological diseases, metabolic disorders, hormonal imbalance, and even cancer in non-target species, including humans. Reproduction, a very selective process that ensures the continuity of species, is affected to a greater extent by the rampant use of insecticides. In females, exposure to insecticides leads to reproductive incapacitation primarily through disturbances in ovarian physiology. Disturbed ovarian activities encompass the alterations in hormone synthesis, follicular maturation, ovulation process, and ovarian cycle, which eventually lead to decline in fertility, prolonged time-to-conceive, spontaneous abortion, stillbirths, and developmental defects. Insecticide-induced ovarian toxicity is effectuated by endocrine disruption and oxidative stress. Oxidative stress, which occurs due to suppression of antioxidant defense system, and upsurge of reactive oxygen and nitrogen species, potentiates DNA damage and expression of apoptotic and inflammatory markers. Insecticide exposure, in part, is responsible for ovarian malfunctioning through disruption of hypothalamic-pituitary-gonadal axis. The current article is focused on the adverse effects of insecticides on ovarian functioning, and consequently, on the reproductive efficacy of females. The possible strategies to combat insecticide-induced toxicity are also discussed in the latter part of this review. Environ. Mol. Mutagen. 61:369-392, 2020. © 2020 Wiley Periodicals, Inc., (© 2020 Wiley Periodicals, Inc.)

In XX v Whittington Hospital NHS Trust [2018] EWCA Civ 2832, the Court of Appeal recognised commercial surrogacy in California as a permissible head of damage in a case of negligently inflicted infertility. Due to changing public policies and judicial opinion regarding the practice, and by incorporating the three-part test of illegality developed for civil claims by the Supreme Court in Patel v Mirza [2016] UKSC 42 into tort law, the Court of Appeal held that the principle of restorative justice required a departure from the precedent established in Briody v St Helens and Knowsley AHA [2001] EWCA Civ 1010., (© The Author(s) 2020. Published by Oxford University Press; All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ethnopharmacological Relevance: Cisplatin (CP) is the classical chemotherapeutic drug for various cancer, but it also accompanies reproductive toxicity and genotoxicity. Liuwei Dihuang Pill (LW) is the traditional Chinese medicine prescription for treating Kidney-Yin deficiency syndrome, which has been reported to prevent and treat various diseases. However, the protective effect of LW on CP-induced reproductive toxicity and genotoxicity has not been reported., Aim of the Study: To investigate the potential protective effect and mechanism of LW on CP-induced reproductive toxicity and genotoxicity in male mice., Materials and Methods: Mice were given LW (0.4, 1.2 and 3.6 g/kg) or Vitamin C (0.1 g/kg) once daily by oral gavage for thirteen consecutive days. Then, CP (3.00 mg/kg) was given intraperitoneal injection once daily for five consecutive days starting on the ninth day. The protective effects of LW against CP-induced reproductive toxicity and genotoxicity were evaluated by body weight, testis ratio, sperm count, sperm viability, sperm abnormal morphology type, micronuclei test, testicular histopathology, serum malondialdehyde (MDA), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) level., Results: The results demonstrated that LW could significantly increase CP-induced the reduction of sperm count and sperm viability, then decrease abnormal sperm type rate and micronucleus rate. Moreover, LW also could improve testicular abnormal histopathologic morphology induced by CP exposure. Meanwhile, LW decreased serum MDA level and increased T-SOD, GSH-Px and CAT level compared to CP group., Conclusion: our findings show that LW has protective effects on CP-induced reproductive toxicity and genotoxicity. LW decreases serum MDA level and increases T-SOD, GSH-Px and CAT level, which indicates that antioxidant activity may be the potential mechanism of LW to resist reproductive toxicity and genotoxicity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Central hypogonadism, also defined as hypogonadotropic hypogonadism, is a recognized complication of hypothalamic-pituitary-gonadal axis damage following treatment of sellar and parasellar masses. In addition to radiotherapy and surgery, CTLA4-blocking antibodies and alkylating agents such as temozolomide can also lead to hypogonadism, through different mechanisms. Central hypogonadism in boys and girls may lead to pubertal delay or arrest, impairing full development of the genitalia and secondary sexual characteristics. Alternatively, cranial irradiation or ectopic hormone production may instead cause early puberty, affecting hypothalamic control of the gonadostat. Given the reproductive risks, discussion of fertility preservation options and referral to reproductive specialists before treatment is essential. Steroid hormone replacement can interfere with other replacement therapies and may require specific dose adjustments. Adequate gonadotropin stimulation therapy may enable patients to restore gametogenesis and conceive spontaneously. When assisted reproductive technology is needed, protocols must be tailored to account for possible long-term gonadotropin insufficiency prior to stimulation. The aim of this review was to provide an overview of the risk factors for hypogonadism and infertility in patients treated for parasellar lesions and to give a summary of the current recommendations for management and follow-up of these dysfunctions in such patients. We have also briefly summarized evidence on the physiological role of pituitary hormones during pregnancy, focusing on the management of pituitary deficiencies., (© 2020 S. Karger AG, Basel.)

Chemotherapy and radiotherapy have increased the life expectancy of cancer patients but may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of treatment on future reproductive autonomy are a major concern. While a few options are open to patients post-puberty, the only option currently open to prepubescent girls is cryopreservation of ovarian tissue and subsequent transplantation. Yet, this procedure raises ethical concerns related to its experimental nature and to risks involved in surgery and general anesthesia. In addition, the risk of malignant cells being reintroduced in the future following autologous transplantation of the ovarian tissue is still poorly evaluated. A number of ethical issues arise surrounding this procedure. While the girl's future reproductive autonomy is at stake, it is important to also consider risks associated with the procedure. Fertility preservation through cryopreservation of ovarian tissue thus raises a conflict between the principles of beneficence and non-maleficence. We argue that the ethical complexity surrounding fertility preservation for prepubescent girls should be resolved by applying the principle of "the child's right to an open future". We propose to consider 'beneficence' through the lens of the reproductive autonomy and her potentialin becoming a genetic parent.

Life expectancy has increased since World War II, and this may be attributed to several aspects of modern lifestyles. However, now we are faced with a downturn, which seems to be the result of environmental issues. This paradigm is paralleled with reduced human fertility, decreased sperm quality, increased premature ovarian failure, and diminished ovarian reserve syndromes. Endocrine disruptor chemicals and other toxic chemicals, herbicides, pesticides, plasticizers, to mention a few, are a rising concern in today's environment. Some of these are commonly used in the domestic setting: cleaning material and cosmetics and they have a known impact on epigenesis and imprinting via perturbation of methylation processes. Pollution from polyaromatic hydrocarbons, particulate matter <10 and <2.5 μm, and ozone released into the air, all affect fertility. Poor food processing management is a source of DNA adduct formation, which impairs the quality of gametes. An important concern is the nanoparticles that are present in food and are thought to induce oxidative stress. Now is the time to take a step backward. Global management of the environment and food production is required urgently to protect the fertility of future generations., (© 2019 Wiley Periodicals, Inc.)

Trans fatty acids (TFAs) are thought to affect reproductive health by causing adverse effects on sperm morphology and ovum quality as a result of changing membrane lipid composition which, in turn, leads to impairment in metabolic pathways. This literature review examines the evidence for the effects of dietary TFAs on male and female infertility. Studies conducted between 2007 and 2017 on the effect of dietary TFAs on human reproductive health and fetal life have been included. They indicate that TFA intakes are inversely proportional to sperm concentration and total sperm count and exhibit a positive correlation with asthenospermia, as well as an adverse association on sperm concentration and semen quality. In the female TFAs intakes are associated with an increase in the risk of ovulatory infertility, adversely affect the length of gestation leading to fetal developmental defects and fetal loss. The findings suggest that high TFA intake (more than 1% of energy consumption) constitute a risk factor for infertility in both sexes.

Introduction: Lead is a multiple organ toxicant and an oxidative-stress inducer. The effect of Costus afer on metal- induced male reprotoxicity has not been previously carried out, hence this study. The present study investigates the protective effect of Costus afer aqueous leave extract on lead- induced reproductive damages in male albino Wistar rats., Methods: Adult male albino Wistar rats were weighed and separated into five groups of five rats each. Groups 1 & 2 served as normal and toxic controls receiving deionized and leaded (CH 3 COO) 2 Pb.3H 2 O and water respectively. Groups 3, 4 and 5 were given 750, 1500 and 2250mg/kg of Costus afer orally, respectively while receiving Pb 2+ water ad libitum for 28 days., Results: The reproductive and antioxidant parameters obtained from the result served as scientific evidence in the study. The result showed non-significant changes in the absolute and relative weights of epididymis and testes in the Pb Group versus the control. Significant increases were recorded in the sperm analysis, blood lead (7.9±1.02; 1.1±0.01) level (BLL), luteinizing hormone (LH) (8.5±1.4:5.5±0.4), and a decrease in follicle stimulating hormone (FSH) (4.5±2.6:6.5±1.65), with non-significant changes in testosterone (TET) (1.3±0.00:1.6±0.2) in the Pb group compared to the control., Conclusion: The treatment with Costus afer exhibited dose-dependent significant changes in testicular oxidative stress, hormonal, sperm analysis and histopathological changes induced by lead. Aqueous leaves extract of Costus afer may be protective against lead induced testicular damage.

The prevalence of male infertility is a well-known public health issue with majority of cases due to deficient sperm production of unknown origin. Studies have associated dietary habits with male factor infertility. Chrysophyllum albidum is a common plant that produces a popular fruit, widely consumed for its nutritional and medicinal values. This study investigates the effects of C. albidum fruit methanol extract on the reproductive functions of male Wistar rats. Ripe C. albidum fruit was extracted using methanol and subjected to phytochemical screening. Fifteen male Wistar rats (100-120 g) divided into three (n = 5) received distilled water (control), 1.0 and 6.4 g kg -1  day -1 extract, respectively, for 28 days via oral gavage. The sperm count, motility, percentage sperm aberration, histology of testes and epididymides were examined by microscopy. Serum levels of luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone were quantified using ELISA. Data were analysed using ANOVA at p < 0.05 significance. Sperm count significantly increased in 6.4 g kg -1  day -1 extract. Serum testosterone level decreased in 1.0 and 6.4 g kg -1  day -1 extract. The architecture of sections of testes and epididymides showed anomalies. C. albidum fruit adversely altered reproductive functions of male Wistar rat., (© 2019 Blackwell Verlag GmbH.)

This study was conducted to determine the effect of turmeric powder dietary supplementation on the histology of visceral organs and reproductive performance of Pseudotropheus acei. The fish were fed dietary additions of 0%, 1%, 3%, 5%, and 7% turmeric powder. Each treatment was replicated three times. There were one male and four female fish with a mean weight of 6 g in each replicate. The fish were fed ad libitum for 90 days. There were no differences in fertility rate, fecundity rate, hatching rate, egg diameter, and larvae survival rate among groups (P < 0.05). Ovulation frequency and the percent of spawning broodstock were less in the 7% and 5% turmeric-supplemented group (P < 0.05), while there were no effects of treatment in the 1%, and 3% groups compared with the control group. Observations in histopathological examinations indicated there were normal tissue structures in the control, 1% and 3% turmeric-supplemented groups, while the addition of 5% and 7% turmeric induced a degeneration of and decrease in number of observable ovarian follicles. In addition, there was a normal liver structure in the control and the 1% and 3% turmeric-supplemented groups and slight to severe lipidosis in the 5% and 7% turmeric-supplemented groups. Also, the supplementation of larger amounts of turmeric induced enteritis and the slight to severe side effects on the relevant organs. These results indicate that supplementing of diets with turmeric powder in amounts of 5% and 7% suppressed ovarian follicle development, and extended periods between times of spawning which resulted in subfertility of broodstocks., (Copyright © 2019. Published by Elsevier B.V.)