DR. ELIRAN MOR, MD

 This study explores how a mother’s physical activity and diet during pregnancy can shape the long-term health of her offspring, using a rat model. We found that swimming during pregnancy helped protect against weight gain in the offspring, but when combined with a high-fat, high-sugar diet after birth, it disrupted important antioxidant defenses in the offspring’s ovaries. These findings highlight the complex impact of maternal habits on the future health of the next generation. Image by Cristiane Matté using BioRender.

 Poor egg (oocyte) quality is a leading cause of reduced fertility in humans and animals. Large vesicles within oocytes appear to be important for oocyte quality in animals but their composition is unknown. Our study has identified that these vesicles, which appear empty in electron micrographs, contain lipid that differs to that contained in classical lipid droplets. This knowledge may be used to improve in vitro maturation media to enhance oocyte quality. Image by K L Reader.

 Bacteria and human spermatozoa share similar surface proteins. This unexpected connection could be key to understanding certain types of unexplained infertility. This study found that a bacterial protein, sperm immobilization factor (SIF), can damage spermatozoa by binding to it. This protein also binds to the bacteria Shigella flexneri. By isolating the SIF binding receptor from Shigella flexneri, this study opens new avenues for treating infertility, offering hope for many affected couples. Diagram by Thomson Soni and Vijay Prabha.

 Understanding the intricate dance of hormones in the ovaries is crucial for women’s health and fertility. This review highlights the roles of two short peptides, endothelin-1 and endothelin-2, which govern the life cycle of the corpus luteum – a key gland for maintaining pregnancy. Our findings reveal that while endothelin-2 promotes the formation of this gland, endothelin-1 triggers its demise, together shedding light on the control and regulation of the reproductive cycle and potential treatments for reproductive disorders. Diagram by Magdalena Szymanska, Raghavendra Basavaraja and Rina Meidan.

 Identifying methods to improve animal health, production, and resilience is critical to create a sustainable food supply to meet global nutritional demand. Recent advancements in gene editing tools, cell culture methods, and in vitro phenotyping can accelerate the identification of variants or novel alleles that are transformative for livestock health and resilience. The use of organoids and gene editing can provide a model to link the genome to the phenome and decrease the number of animals needed for research. Image by Eun Su Jeon and the University of Missouri Molecular Cytology Core.

 We acknowledge the Traditional Owners of the land, sea and waters, of the areas that we live and work on across Australia. We acknowledge their continuing connection to their culture, their contribution to our shared knowledge, and pay our respects to their Elders past and present.

 BMJ Sexual & Reproductive Health is an international journal that promotes evidence-informed practice for contraception, abortion and all aspects of sexual and reproductive health. The journal publishes research papers, topical debates and commentaries to shape policy, improve patient-centred clinical care, and to set the stage for future areas of research. It is the official journal of the Faculty of Sexual and Reproductive Healthcare.

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 Infertility affects 1 in 6 people1. With 1/3 of infertility problems caused by female factors, 1/3 male factors, and 1/3 that remains unexplained or due to both partners2, or factors that cannot be determined, every situation is unique. While nearly 56% of those facing infertility reach out for help, only 22.4% get the specialised care they need for treatments like in vitro fertilisation (IVF)3. That’s why having a well-rounded fertility team is so important. This group—made up of fertility specialists, nurses and other experts—works together to provide the personalised support and advice that can make all the difference in someone’s journey to parenthood. By teaming up, they can help to tackle the ups and downs of infertility, offering hope and practical solutions to those looking to start or grow their families.

 Knowing when to visit a reproductive health professional can make a big difference in starting the journey towards parenthood. If a couple has been trying to conceive for 12 months without success—or for 6 months if they are over 35—it’s a good idea to seek help11.

 Women should also visit a doctor if they have irregular, absent, or painful periods, have experienced one or more miscarriages, or show symptoms of conditions like endometriosis or polycystic ovary syndrome (PCOS)5. For men, it's important to consult an andrologist if they’re facing any sexual health issues, urological conditions, or hormonal imbalances that could affect fertility12.

 On the path to fertility treatment, a team of professionals — like fertility specialists, nurses, embryologists, and andrologists—come together to offer holistic care. Each specialist brings their own expertise, making sure every part of the fertility journey is supported. From diagnosing the cause of infertility to guiding you through treatments like IVF, this multidisciplinary approach helps to tailor the treatment plan to each person’s unique needs.

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 The Journal of Family and Reproductive Health (JFRH) is the quarterly official journal of Reproductive Health Research Center, Tehran University of Medical Sciences. This journal features fulllength, peer reviewed papers reporting original research, clinical case histories, review articles, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology including genetics, endocrinology, andrology, embryology, gynecologic urology, fetomaternal medicine, oncology, related infectious disease, public health, nutrition, surgery, menopause, family planning, infertility, psychiatry–psychology, demographic modeling, perinatalogy–neonatolgy ethics and social issues, and pharmacotherapy. A high scientific and editorial standard is maintained throughout the journal along with a regular rate of publication.

 Maria Isabel do Nascimento , Lara Miranda Marchesi ORCID , Wender Emiliano Soares ORCID , Jenaine Rosa Godinho Emiliano ORCID , Maria Auxiliadora Nogueira Saad ORCID , Glaucimara Gonzaga Nunes Hacar ORCID , Gabriel Eijiro Chiracava ORCID

 Fatemeh Golshahi ORCID , Fatemeh Rahimi-Sharbaf ORCID , Mahbobeh Shirazi , Sara Saeedi , Athar Abdolrazagh Nejad , Sahar Garfami , Nafise Saedi , Jafar Golshahi ORCID , Zeynab Amiriarya , Narjes Tavakolikia , Behrokh Sahebdel ORCID

 Approximately 10 to 15% of couples are impacted by infertility. Recently, the pivotal role that lifestyle factors play in the development of infertility has generated a considerable amount of interest. Lifestyle factors are the modifiable habits and ways of life that can greatly influence overall health and well-being, including fertility. Many lifestyle factors such as the age at which to start a family, nutrition, weight, exercise, psychological stress, environmental and occupational exposures, and others can have substantial effects on fertility; lifestyle factors such as cigarette smoking, illicit drug use, and alcohol and caffeine consumption can negatively influence fertility while others such as preventative care may be beneficial. The present literature review encompasses multiple lifestyle factors and places infertility in context for the couple by focusing on both males and females; it aims to identify the roles that lifestyle factors play in determining reproductive status. The growing interest and amount of research in this field have made it evident that lifestyle factors have a significant impact on fertility.

 It has been estimated that 7.4% of women and their husbands in the United States are infertile [1] and that the number of infertile people in the world may be as high as 15%, particularly in industrialized nations [2]. Decreasing the number of people affected by infertility has become a top priority for many health organizations, including Healthy People 2020 [3]. Lifestyle factors can be modified to enhance overall well-being and they are ultimately under one’s own control. They play a key role in determining reproductive health and can positively or negatively influence fertility.

Dr Mor

 The goal of this review is to demonstrate the potential effects of multiple lifestyles on reproductive health for both men and women. The review focuses primarily on modifiable lifestyles including the age when starting a family, nutrition, weight management, exercise, psychological stress, cigarette smoking, recreational drugs use, medications, alcohol use, caffeine consumption, environmental and occupation exposure, preventative care, clothing choices, hot water, and lubricants. While many aspects of life are not modifiable, lifestyles may be changed.

 The age of a man or woman is a factor among others that can affect fertility. Due to pursuit of education and other factors, many couples are choosing to delay child-bearing. Fertility peaks and then decreases over time in both men and women, thus the reproductive timeline may be one aspect to consider when determining the ideal time to start a family. As men age, testosterone levels begin to decrease and hypogonadism results. However, if testosterone is used to treat hypogonadism, it can suppress spermatogenesis [4]. Semen parameters also begin a steady decline as early as age 35 [5]; semen volume and motility both decrease and morphology may become increasingly abnormal [4,6]. After the age of 40, men can have significantly more DNA damage in their sperm, as well as decline in both motility (40%) and viability (below 50%) (n = 504, p < 0.001) [7]. There may also be an increase in time to pregnancy with an increase in male age [8]. Hassan and Killick reported that when men were over the age of 45, their partner’s relative risk of an increase in time to pregnancy over one year increased to 4.6, and over two years increased to 12.5 (n = 1832, CI = 24.5-38.1) [9]. The authors also noted that the older population tended to consume more alcohol, have intercourse less often, had longer contraceptive usage, and smoked less cigarettes which could have been confounding factors. Another study found that there are also exponentially fewer infants born to fathers ≥35 to 39 years of age and older compared to younger age groups even when controlling for female age (n = 122,061) [10].

 The reproductive timeline for women is complex. A woman is born with all the oocytes she will ever have, and only 400–500 are actually ovulated [6]. As the number of oocytes decline, a woman’s menstrual cycle shortens, infertility increases, and menstrual irregularity begins 6–7 years before menopause. Increasing age increases a woman’s time to pregnancy. When under the age of 30, a woman’s chances of conceiving may be as high 71%; when over 36, it may only be 41% [8]. The chances of becoming pregnant and being able to maintain a pregnancy are also affected. Matorras et al. reported that in a population of women, the number of infants born begins to exponentially decrease after the age bracket of 35–39 (n = 89,287) [10]. The odds of becoming pregnant and maintaining a pregnancy are believed to be connected to numerous factors, including euploidy. Euploidy has been found to be inversely correlated with female age (P < .01; n = 544) [11]. Another study reported that the rate of aneuploidy for women over 35 was 45.7% versus 34.8% for women under 35 (n = 352, p = .018) [12]. In comparison, Munné et al. reported the rates of euploidy decrease 50% for women under 35, decrease 40% for women between the ages of 35 and 40, and decrease 33.3% for women over 40 [13]. In addition, chromosomal abnormalities and aneuploidy may increase the risk of spontaneous abortion and implantation loss with increasing age [4,6]. Overall, women’s fertility is significantly lower in the 30s and 40s [6].

 Aspects of a male’s diet may have an impact on his fertility. Consuming a diet rich in carbohydrates, fiber, folate, and lycopene [14] as well as consuming fruit (OR 2.3) and vegetables (OR 1.9) [15] correlates with improved semen quality. Consuming lower amounts of both proteins and fats were more beneficial for fertility [14]. Another potential benefit could be antioxidants, which play a pivotal role in the body by scavenging reactive oxygen species (ROS). Reactive oxygen species or ROS are a collection of free radicals and non-radical derivatives of oxygen such as superoxide anion (O2• -), hydrogen peroxide (H2O2), hydroxyl radical (OH•). This category also includes free radicals derived from nitrogen called reactive nitrogen species such as: nitric oxide (NO•), nitric dioxide (NO2•), peroxynitrite (ONOO-). Collectively they are termed as reactive oxygen species. These are by-products of cellular respiration that are necessary for certain cellular activity, including sperm capacitation; however, an overabundance of ROS may compromise sperm function, including sperm motility, altering DNA and decreasing membrane integrity [16]. Antioxidants are molecules such as albumin, ceruloplasmin, and ferritin; and an array of small molecules, including ascorbic acid, α-tocopherol, β-carotene, reduced glutathione, uric acid, and bilirubin or enzymes superoxide dismutase, catalase, and glutathione peroxidase. Antioxidants help remove the excess ROS in the seminal ejaculate and assist in the conversion of ROS to compounds that are less detrimental to cells. If there is more ROS than the local antioxidants can remove, it results in oxidative stress. Oxidative stress can result in sperm protein, lipid and DNA damage and sperm dysfunction [16]. However, there have been some disputes when it comes to research outcomes. Mendiola et al. demonstrated that vitamin C, but neither vitamin E nor selenium, had significant effects on semen quality (n = 61, p < 0.05) [14]. A high amount of antioxidants has been demonstrated to increase semen quality, compared to low or moderate amounts [17]. Another study reported that vitamin E and selenium decreased levels of malondialdehyde (MDA), a marker for damage done by reactive oxygen species, more so than did vitamin B [18]. Suleimen reported that Vitamin E decreased MDA levels, increased spermatozoa motility, and led to 21% couples conceiving over a 2.5 year period versus no conceptions in men who took a placebo (n = 52) [19]. An article reviewing previous studies on antioxidants concluded almost every study conducted pertaining to DNA damage and oxidative stress revealed that antioxidants caused significant improvement, particularly in asthenospermic patients [20]. A Cochrane review including 34 studies, determined that men who use oral antioxidants had a significant increase in live birth rate (OR 4.85; CI 1.92-12.24; P = 0.0008; n = 214) when compared to control [21]. Antioxidants were also associated with a significant increase in pregnancy rate when compared to control (OR 4.18; CI 2.65-6.59; P < 0.00001; n = 964) [21].

 A woman’s diet may ultimately affect her fertility, particularly ovulation. Overall, replacing carbohydrates with animal protein was demonstrated to be detrimental to ovulatory fertility (OR 1.18) [22]. Adding just one serving of meat was correlated with a 32% higher chance of developing ovulatory infertility, particularly if the meat was chicken or turkey [22]. However, replacing carbohydrates with vegetable protein demonstrated a protective effect (OR 0.5) [22]. Choosing trans fats in the diet instead of monounsaturated fats has been demonstrated to drastically increase the risk of ovulatory infertility (RR 2.31) [23]. Consuming trans fats instead of carbohydrates correlated with a 73% increase in risk of ovulatory disorder (RR 1.73) [23]. The use of multivitamins and supplements also has an effect. Women who take multivitamins may be less likely to experience ovulatory infertility; women who take six or more tablets had the lowest relative risk for infertility (RR 0.59) followed by women who took three to five (RR 0.69), and two or less (RR 0.88) [24]. Chavarro et al. found that women with high “fertility diet” scores emphasized by a higher monounsaturated to trans-fat ratio, vegetable over animal protein, high-fat over low-fat dairy, a decreased glycemic load, and an increased intake of iron and multivitamins had lower rates of infertility due to ovulation disorders (p < 0.001) [25].

 An individual’s weight is often associated with his or her eating habits and amount of activity. Body mass index (BMI) is reported as a number. If it is below 18.5 it is considered underweight, between 18.5 and 24.9 is normal, above 25 is overweight, and over 30 is considered obese [26]. Body weight can have significant effects on health, including cardiovascular disease, diabetes, and infertility [27].

 The obesity epidemic has recently become is a serious issue, particularly in industrialized nations. The goal set by Healthy People 2010 of reducing obesity in the United States to 15% was not met [28]. In fact, adult obesity increased to 35.7% in 2010 [29]. The rising number of obese individuals may be due in part to an energy-rich diet as well as insufficient physical exercise [30]. In addition to other potential health risks, obesity can have a significant impact on male and female fertility.

 The proportion of men over 20 years of age in the U.S. that are obese has risen to 35.5% [29]. BMI may be a significant factor in fertility, as an increase in BMI in the male by as little as three units can be associated with infertility (OR 1.12) [31]. Obese men are three times more likely to exhibit a reduction in semen quality than men of a normal weight [32]. Several studies have demonstrated that an increase in BMI is correlated with a decrease in sperm concentration [33,34], and a decrease in motility [35]. Overweight men have also been found to have increased DNA damage in sperm [36,37].

 A relationship also exists between obesity and erectile dysfunction (ED). Corona et al. reported that 96.5% of men with metabolic syndrome presented with ED (n = 236) [38]. ED may be the consequence of the conversion of androgens to estradiol. The enzyme aromatase is responsible for this conversion, and is found primarily in adipose tissue [39]. As the amount of adipose tissue increases, there is more aromatase available to convert androgens, and serum estradiol levels increase [36,39]. Other hormones including inhibin B and leptin, may also be affected by obesity. Inhibin B levels have been reported to decrease with increasing weight, which results in decreased Sertoli cells and sperm production [40]. Leptin is a hormone associated with numerous effects including appetite control, inflammation, and decreased insulin secretion [41]. A study conducted in mice demonstrated that leptin was nearly five times higher in obese mice than lean mice, and that the higher leptin levels corresponded to five times lower fertility in the obese mice [41]. It was also noted that there was a down regulation of the leptin receptors located on the testes, possibly indicating that leptin resistance could play a role in male infertility [41].

 In 2010, 35.8% of women in the U.S. over the age of 20 were considered obese [29]. Women with a BMI over 30 have longer time to pregnancy than women who have a BMI between 20 and 25, although this trend was not significant, and the study was conducted via a questionaire (n = 2,472) [8]. In a systematic review, Boots & Stephenson reported a miscarriage rate of 10.7% in women with a normal BMI, which was significantly lower than that of 13.6% in obese women (OR: 1.31; 95% CI 1.18-1.46) [42]. Furthermore, obese women had a higher rate of recurrent, early miscarriage compared to non-obese women. There is evidence that miscarriage in obese women may not necessarily be due to the karyotype of the developing fetus. Overweight and obese women under the age of 35 were found to have lower rates of aneuploidy, suggesting that miscarriage may be due to other influences such as endometrium receptiveness [12,43]. Additionally, Bellver et al. found a negative correlation between increasing BMI and implantation (r2 = .03, P = .008) [44]. A decreased ongoing pregnancy rate of 38.3% per cycle was also found in women who were overweight in comparison to the 45.5% in non-overweight women (n = 2656) [44]. There is speculation that these negative outcomes may be related to follicular environment, which differs in women who are obese compared to normal weight women. Some of the differences may include an increase in follicular fluid levels of insulin, lactate, triglycerides, and C-reactive protein; there may also be decreases in SHBG [45]. The negative effects of obesity on fertility in women may be reversible. Clark et al. found that after losing an average of 10.2 kg, 90% of obese previously anovulatory women began ovulating [46].

 Obesity is not the only way in which weight can impact fertility. Men who are underweight are also at risk of infertility. Men who are underweight tend to have lower sperm concentrations than those who are at a normal BMI [36]. As the majority of the available literature focuses on the impact of obesity, more research is needed into the effects that being underweight may have on male fertility.

 For women, being underweight and having extremely low amounts of body fat are associated with ovarian dysfunction and infertility [47]. Additionally, the risk of ovulatory infertility increases in women with a BMI below 17 (RR 1.6) [48]. A meta-analysis of 78 studies, which included 1,025,794 women, found that underweight women had an increased risk of pre-term birth (RR 1.29) [49]. Eating disorders such as anorexia nervosa are also associated with extremely low BMI. The lifetime prevalence of anorexia nervosa in women is 0.9%, with the average age of onset being 19 years old [50]. Although relatively uncommon, eating disorders can negatively affect menstruation, fertility, and maternal and fetal well-being [51]. It was found that among infertile women suffering from amenorrhea or oligomenorrhea due to eating disorders, 58% had menstrual irregularities (n = 66) [51]. Freizinger et al. reported 20.7% of infertile women seeking intra uterine insemination (IUI) had been diagnosed with an eating disorder, suggesting that women with history of eating disorders may be at a higher risk for infertility [52].

 A healthy amount of exercise in men can be beneficial. Physically active men who exercised at least three times a week for one hour typically scored higher in almost all sperm parameters in comparison to men who participated in more frequent and rigorous exercise (n = 45) [53]. Moderately physically active men had significantly better sperm morphology (15.2%), the only ones to be ranked above Kruger’s strict criteria in comparison to the men who played in a competitive sport (9.7%) or were elite athletes (4.7%) (P < .001). Other parameters including total sperm number, concentration, and velocity also showed a similar trend but were not nearly as marked [53]. Bicycling more than five hours per week has been demonstrated to have a negative correlation with both total motile sperm counts (OR 2.05) and sperm concentration (OR 1.92) [54]. Diet combined with exercise in obese male rats has been shown to increase both sperm motility (1.2 times) and sperm morphology (1.1 times), and to decrease both sperm DNA damage (1.5 times) and reactive oxygen species (1.1 times) (n = 40; P < .05) [55].

 Physical activity has been shown to confer a protective effect on fertility when coupled with weight loss in obese women [46]. However, excessive exercise can negatively alter energy balance in the body and affect the reproductive system [56]. When energy demand exceeds dietary energy intake, a negative energy balance may occur and may result in hypothalamic dysfunction and alterations in gonadotropin-releasing hormone (GnRH) pulsality, leading to menstrual abnormalities, particularly among female athletes [57]. Increased frequency, intensity, and duration of exercise were found to be significantly correlated with decreased fertility in women, including an OR of 3.5 for infertility in women who exercised every day (n = 24,837) [58]. A study examining 2,232 women undergoing in vitro fertilization (IVF) found that women who engaged in cardiovascular exercise for 4 hours or more per week for as little as one year prior to the treatment had a 40% decrease in live birth rate (OR .6; 95% CI .4-.8), as well as higher risks of cycle cancellation (OR 2.8; 95% CI 1.5-5.3) and implantation failure (OR 2.0; 95% CI 1.4-3.1) [59]. Wise et al. also found a significant positive dose–response relationship between vigorous activity and time to pregnancy [60]. However, moderate physical activity was determined to be weakly correlated with increases in fecundity, independent of BMI.

 Stress is a prominent part of any society, whether it is physical, social, or psychological. Infertility itself is stressful, due to the societal pressures, testing, diagnosis, treatments, failures, unfulfilled desires, and even fiscal costs with which it is associated [61].

 Males who experienced more than two stressful life events before undergoing infertility treatment were more likely to be classified below WHO standards for sperm concentration, motility, and morphology [62]. In a study including 950 men conducted by Gollenberg et al., stress such as a job, life events, and even social strain were seen to have a significant impact on sperm density (log scale, β = −0.25; CI −0.38 to −0.11), total sperm counts (log scale, β = −0.30; CI −0.45 to −0.15), forward motility (OR 1.54; 95% CI 1.04-2.29), and morphology (OR 1.93; 95% CI 1.02-3.66) [63]. Semen parameters may potentially be linked to stress. Stress and depression are thought to reduce testosterone and luteinizing hormone (LH) pulsing [62,64], disrupt gonadal function [64], and ultimately reduce spermatogenesis and sperm parameters. It has yet to be determined if depression causes low testosterone, or if low testosterone can cause depression [65]. Although there appears to be a relationship between stress and infertility, it is uncertain which is the cause and which is the effect. The perceived stress of providing a semen sample was reported to be negatively linked to overall semen quality with a 39% decrease in sperm concentration, 48% decrease in motility, and worse overall semen parameters on the day of oocyte retrieval, although there was no change in either volume or morphology [66,67].