Dr Eliran

 One recent qualitative study with British adolescents (ages 16–18) and emerging adults (ages 21–24) demonstrated that these age groups wanted the knowledge but had a hard time integrating it without worrying about the implication for them in the present or future. While these young people had knowledge, its breadth and depth were not enough for them to make informed decisions. The subjects reported that they saw no point to the knowledge at a stage of life when family building was not on their minds. The researchers speculated that the content, amount, and timing of FA information needs to be tailored to the developmental stage of the learners. They conclude “Young people welcome fertility information but qualitative data illustrate the need for it to be tailored to specific age groups to maximize its benefits and ensure young people can integrate the information they need to maintain reproductive health and make informed decisions about future parenthood [53].” While the sample size was small (n=33), the findings hint at the complexity of providing useful and meaningful FA information.

 Important sex discrepancies do exist. One study found that Canadian men aged 18–50 have poor knowledge regarding male infertility [54]. About half of men (51%) correctly identified male infertility-related risk factors and 45% could identify health-related issues. Of the men studied, 58% reported wanting more information about male infertility and reproductive health and they preferred two sources for that information, medical professionals and online sources [54]. It is not a surprise that men have low knowledge about infertility or infertility risk factors; young men’s awareness and knowledge about issues such as female birth control methods is not much better—they have low awareness of highly effective female contraception methods as compared to condoms and shorter-acting female birth control methods (pills, patch) and have very poor knowledge about any form of female contraception methods other than condoms [55].

 A recent United States study found that about 60% of men are in need of preconception care. In general, male preconception care focuses on conception prevention. As the authors note, preconception care requires reproductive aged persons to have “high reproductive awareness.” In other words, a plan that includes what is necessary to prevent an unintended pregnancy as well as create optimal health conditions prior to a desired pregnancy. They note that women have been the primary focus of such improvement efforts [56]. The men in that study varied on multiple factors, including age, locale, ethnicity, and poverty level, among other variables. A significant number of men in the study had health risks that could impair reproductive capacity. Poor health status, overweight or obesity, daily marijuana use, binge drinking, addictive drug use, and high STI risk were some of the factors found in this study. Significant numbers of these men had usual sources of care (71%), health insurance (76%), and a yearly physical exam (49%). At the same time, among all men in the study, healthcare provider counseling in the preceding year was reported by 11% for STIs; 10% for HIV; and 10% for contraception, highlighting the gap between observed need for care and actual delivery of the services.

 Women had greater FA in 12 of the studies reviewed before. At the same time 10 studies found no difference between women’s and men’s FA. Some studies reported mixed results [50]. There are probably good reasons for women’s greater awareness that will be discussed later. One of the significant findings from the review is that while people are aware of the risk age plays in reduced fertility, they overestimate the age at which declines begin. They also overestimate the probability of becoming pregnant either spontaneously or via fertility treatment. The authors suggest that the focus on pregnancy prevention in school-based sexuality education is a contributing factor to this finding.

 When it comes to men’s help seeking for infertility concerns, help seeking was quite low, especially for younger men. For example, although infertility prevalence was slightly lower for males aged 16–24 (4%) and 25–24 (9%) as compared to older aged men, only 14% of men aged 16–24 sought help as compared to 50% of men aged 24–34 and 57% of men aged 35–44 [57].

 Although many conditions place children and youth at risk for infertility, including males, many youth may not be aware of conditions that occurred earlier in childhood (e.g., anorchia, testicular torsion) or conditions that may not present until adolescence (Klinefelter syndrome, Kallman syndrome) [58]. Even among males with cancer, the prevalence of help seeking for men with infertility is low. For example, the prevalence of male infertility prevalence in the Childhood Cancer Survivor Study was 46% among cancer survivors as compared to 18% in the sibling comparison group, but only 54% went for infertility care as compared to 21% of the sibling comparison group [59]. Another study that conducted a medical record review of males aged 13 with a new cancer diagnosis found that only 29% received fertility counseling and only 11% attempted sperm banking [60].

 In 2006 the CDC published recommendation guidance to improve both preconception health and care with the goal to improve the health of women and couples, before conception of a first or subsequent pregnancy [61]. One of the key recommendations is that individuals take responsibility across the lifespan, and, specifically, each woman, man, and couple should be encouraged to have a reproductive life plan and use a lifespan approach to focus individual attention on reproductive health to reduce unintended pregnancies, age-related infertility, fetal exposures to teratogens, and to improve women’s health and pregnancy outcomes. In 2014 updates to the nation’s Title X guidelines by the Office of Population Affairs and the CDC incorporated these guidelines along with additional guidance to make comprehensive clinical care guidelines for women and men related to family planning and SRH care, including need for basic infertility counseling as an important component [62]. These guidelines are separate but parallel to women’s health guidance that was implemented as part of the Patient Protection and Affordable Care Act (ACA) [63] A similar emphasis on the SRH needs of men had not existed. Between 2011 and 2014 several agencies collaborated to create them for the first time for the United States. It has been noted that development of guidelines for men is critical for a variety of reasons, including the health of their partners, including men in family planning, and improving the fathering capacity of men. An additional desired outcome is the need to integrate men’s healthcare into reproductive health programs nationwide [64]. As documented elsewhere, public awareness as well as research about male infertility is substantially missing [65,66].

 More recent guidelines published in 2018 by the American Academy of Pediatrics (AAP) promote counseling at-risk pediatric populations about fertility and sexual function beginning in infancy with parents or at earliest time point a patient may be affected [67]. This guidance contributes to other condition-specific guidance in 2008 by the AAP (referring patients at risk for fertility loss primarily focused on childhood cancer for fertility preservation (FP) before gonadotoxic therapy) and in 2006 by the Pediatric Endocrine Society (disclosing to youth with disorders of sex development about their condition and counseling about fertility and sexual function, using “collaborative, ongoing” approach) [68,69].

 Despite the guidelines aforementioned, FA among women of reproductive age in the United States, including medical trainees, is low. The data, collected with a validated measure, indicate that even trainees in obstetrics and gynecology have gaps in their knowledge of natural fertility and infertility treatment [70]. Others have noted that fertility knowledge in groups likely to delay childbearing is lacking [71]. Participants in these studies typically overestimate pregnancy probability with increasing age as well as the success rate of ARTs. Multiple studies report similar findings [52,72]. Many of these studies have surveyed populations that are overwhelmingly white and primarily female.

 Several studies have specifically evaluated college students of Latin origins or those living in Mexico [73,74]. One study of Latino college students at a midwestern United States university found that cultural issues, including shame and privacy regarding matters related to sex kept them from considering or talking about infertility [74]. This group did not see infertility as a medical problem that could be resolved, in part due to the high cost of ART. The authors surmise that some help seeking for fertility problems takes place outside customary Western medical models due to infertility’s suggestion of traditional gender role failure for both sexes.

 The second study, conducted in Mexico, demonstrated poor FA for both men and women. Most participants believed it would be easy to become pregnant at a later age. For example, the great majority thought a woman’s fertility did not significantly decline until age 40. The authors note that this misinformation places young people at risk for involuntary childlessness due to delaying childbearing. They also were surprised at the high percentages of both men and women who had no intention to have children, 48% for women and 59% for men [73].

 Barriers in providing fertility care have been described among care providers who are seeing patients most at risk. For example, despite most oncologists agreeing that pubertal cancer patients be offered fertility referral (84%), only 46% referred their male patients to fertility specialist before treatment more than 50% of the time [75]. Despite most oncologists demonstrating knowledge of FP and discussing and describing they feel comfortable discussing FP, only half (55%) referred their patients to an infertility specialist. Barriers to discussing FP identified by clinicians in this study included the perception that patients were too ill to delay care, patients were already infertile from prior therapy, time constraints, and inadequate access to infertility specialists [76].

 One recent literature synthesis identified five themes influencing providers’ FP discussions with young cancer patients: lack of knowledge about guidelines, costs, where to refer, conducting informed consent with minors and parents, how to have these discussions; lack of comfort and being embarrassed to talk about sex and masturbation; patient-related factors such as being less likely to talk with young patients, beliefs that patients cannot afford procedures, who should be involved in conversation, and being more likely to discuss it if the patient brings it up; parent-related factors, including ethical concerns about parent involvement; and the lack of educational materials to share with patients and families [77].

 Development of more age and sex developmentally appropriate materials are also needed. For example, one program in Canada used an evidence-based approach to develop informational brochures in plain language with patients and families for understanding the process of sperm banking for teens with cancer [60]. Similar approaches can also be developed for engaging parents of at-risk youth, partners of at-risk individuals, and gatekeeper clinicians. Finally, for some populations strategies may be needed to account for the lack of socialization around healthcare use, especially among men, that require healthcare system modifications that can better meet needs of boys and men throughout the life course [78,79].

 Ulcerative colitis commonly affects patients during their reproductive years, therefore issues related to contraception, fertility, pregnancy, delivery, and breastfeeding are significant concerns. Survey studies suggest that patients fear that the disease itself or the medical therapies for ulcerative colitis may reduce fertility, the course and outcome of pregnancy, mode of delivery, fetal development, and the safety of breastfeeding. Patients also worry that pregnancy may worsen their disease course.11 There is also concern among women with IBD about the heritability of IBD and the potential inability to care for a child given their disease activity. These concerns likely contribute to the relatively high rates of voluntary childlessness among women with IBD.12 Walldorf and colleagues13 describe that females over the age of 35 with IBD had significantly higher rates of childlessness than the general population (36.7 vs 22.9%; OR, 1.9; P<.001). Similarly, in another study of 169 patients, voluntary childlessness in females with ulcerative colitis was nearly 2 times higher than the general population (14% vs 6.2%; P = .08).14

 Despite the potential patient fears and concerns described, several studies have reported no decrease in fertility in females with well-controlled ulcerative colitis who have not undergone surgery, as compared with those without IBD.15,16 In a systematic review of 6 studies on fertility in ulcerative colitis, 2 small studies suggested a reduced fertility rate owing to voluntary childlessness; the remaining studies did not report any difference in fertility rates between females with ulcerative colitis and those without the disease.15 Furthermore, studies have reported that voluntary childlessness in patients with IBD decreases after counseling from health care professionals regarding reproductive issues.11

 Although patients without a history of surgery with well-controlled disease have similar fertility rates as the general population, certain factors may negatively influence fertility in females with ulcerative colitis. For example, abstinence or decreased sexual activity owing to symptoms or the fear of symptoms, the presence of active inflammatory disease, or a history of surgery may negatively affect fertility.

 An estimated 10% of patients with ulcerative colitis will require surgery in their lifetime.17–19 Although fecundity in female patients with ulcerative colitis is similar to controls before undergoing surgery, studies report a decrease in fecundity after surgical treatment of ulcerative colitis. One retrospective study of 343 females with ulcerative colitis evaluated the months of unprotected sex leading up to pregnancy or the inability to conceive to estimate the fecundability ratio in patients with ulcerative colitis before diagnosis, after diagnosis, and after undergoing restorative proctocolectomy with IPAA. This study found that the fecundability ratio was not decreased in females with ulcerative colitis before diagnosis (fecundability ratio, 1.46; P = .002) or after diagnosis (fecundability ratio, 1.01; P = NS) as compared with females in the reference population. However, fecundability ratio was decreased after colectomy with IPAA (fecundability ratio, 0.20; P<.0001).20 A meta-analysis reported that females who underwent IPAA had a 3 times greater risk of infertility. This study reported infertility rates of 14% for medically treated patients and rates of 48% in those who had undergone IPAA.21

 The cause of impaired fertility after IPAA is unknown, but potential factors include surgical manipulation in the pelvis or adhesions resulting in damage to the reproductive organs after extensive pelvic dissection.3 A study of females with familial adenomatous polyposis reported that fecundability was decreased to 54% (P = .015) after proctocolectomy with IPAA, but that the fecundability of females who underwent subtotal colectomy with ileorectal anastomosis (IRA) was not different from the general population.20,22 This may be because IRA does not involve extensive pelvic dissection. Importantly, IRA is only an option for patients with normal anal sphincter tone, lack of severe perianal or rectal disease, and no concern for dysplasia or cancer.17 Because of the negative effect of surgery on fertility, some females of childbearing potential who require surgical treatment for ulcerative colitis may elect for temporary diverting ileostomy or temporary IRA until childbearing is complete before creation of IPAA.3 More recently, a study reported that a laparoscopic approach to surgery might decrease these risks. A small survey study reported that in patients who underwent laparoscopic IPAA, 70% were able to become pregnant spontaneously, as compared with 39% of those who underwent IPAA via an open approach.17,23 Although larger trials have not confirmed this finding, a laparoscopic approach may benefit patients who desire future pregnancy.

Eliran

 Although patients report fear of potential negative effects of medical therapy on fertility or pregnancy, the vast majority of medications for ulcerative colitis do not effect fertility and are considered low risk in pregnancy17 (Table 1). In females, 2 exceptions are methotrexate and thalidomide, which are absolutely contraindicated in pregnancy given risk of teratogenicity. In males, some medications have been associated with a decrease in fertility: sulfasalazine and methotrexate can cause reversible oligospermia and sulfasalazine has also been associated with reduced sperm motility and abnormal sperm morphology.15 Given limited data on females attempting pregnancy who are treated with Janus kinase inhibitors such as tofacitinib, providers should recommend avoidance of this class of medication during conception and pregnancy.

 The presence of active endoscopic disease may impact fertility. In a large cohort study of 9639 females with IBD, there were lower fertility rates in females with IBD in periods after flares as compared with females with IBD without disease flares, suggesting that active disease may impact fertility.16 Proposed mechanisms include associated inflammation in adjacent organs or decreased sexual activity in patients with active symptoms. Furthermore, malnutrition, anemia and depression in the setting of flares may also impact fertility.17 Notably, conceiving in the setting of active disease has been associated with worse pregnancy outcomes, thus it is recommended that females with IBD maintain remission for 3 to 6 months before conception.24

 Because the presence of active disease in the setting of pregnancy increases maternal and fetal risks, it is ideal for patients with ulcerative colitis to conceive after achieving remission, if pregnancy is desired. Additionally, certain therapies (eg, methotrexate) are teratogenic and should be avoided in pregnancy. For these reasons, family planning in patients with ulcerative colitis can improve outcomes, and many options for contraception exist, including progestin only long-acting hormonal methods (eg, intrauterine devices or implants), progestin-only short-acting methods (eg, depo-medroxyprogesterone and progesterone only pills), short-acting combined hormonal contraceptives (eg, pills, transdermal patch, or vaginal ring), long-acting nonhormonal method (eg, Copper intrauterine device), nonreversible methods (eg, permanent sterilization), and barrier methods.

 When selecting a contraceptive method, consideration should be given to the effectiveness of the method as well as patient preference for one modality over another (Table 2).25 There are concerns from both patients and providers about certain methods of contraception and IBD. One consideration is the potential for malabsorption of oral contraceptive pills. Although theoretically extensive small bowel resection or severe disease may lead to malabsorption, studies have suggested that neither colectomy26,27 nor limited ileal resection28 significantly change absorption.25 Concern has also been raised about the potential for oral contraception to increase the risk of IBD flares. However, the majority of studies have not supported this association.9,25

 Another consideration is the risk of venous thromboembolism (VTE) in patients with IBD on estrogen-containing oral contraception. Studies report a 2- to 3-fold increase in VTE in females with IBD, with a 3- to 8-fold increase in the setting of active disease.29 The proposed mechanism of this is through an estrogen-driven increase in the hepatic production of serum globulins involved in the coagulation cascade.25 In the general population, studies have reported a 2-fold increase in VTE in females using an estrogen-based method such as combination pills, the patch, or the ring,30,31 but not progestogen-only pills or hormonal releasing intrauterine devices.25,32 Data regarding the specific risk of VTE in females with IBD using estrogen-based contraception are lacking. However, given the theoretic risk of VTE, consideration could be given to avoiding estrogen-containing methods in females with IBD who are at higher risk of VTE.

 Studies demonstrate an increased risk for active disease during pregnancy if active disease is present at conception.33 Because active disease in pregnancy is associated with a higher risk of complications, it is important to counsel patients on the importance of achieving remission even before conception. Additionally, patients with IBD may have misperceptions about safety of medications during pregnancy and may discontinue or decrease their medications once they conceive, which increases the risk of IBD flare. For these reasons, preconception counseling for patients with IBD is essential, and can optimize disease control during conception and throughout pregnancy with the goal of reducing disease-related maternal and birth complications. We recommend that patients undergo endoscopic restaging before conception with the goal of endoscopic remission at time of conception. In addition to preconception counseling by the gastroenterology provider, all patients with IBD should have a consultation with a high-risk obstetrician or maternal and fetal medicine provider to discuss the routine management of ulcerative colitis during pregnancy, the safety of medical therapy, and a management plan in case bowel disease worsens in the setting of pregnancy.

 Rates of infertility, defined as the inability to conceive within 1 year of having unprotected intercourse, in people with ulcerative colitis are overall similar to the general population. For those females with ulcerative colitis who are unable to conceive, studies suggest that infertility treatments (such as in vitro fertilization) are successful at similar rates to the general population,34 including in those patients with a history of IPAA.35

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 More couples are delaying childbearing, which unfortunately can negatively influence the health of their child. Using reproductively old mice at 12 months old, we examined the characteristics of the offspring of older mothers at birth, and then followed them to adulthood and measured markers of adult health, namely growth, glucose tolerance, immune function and behaviour. This study provides insights into how maternal age influences the health and development of their offspring. Image by Macarena B. Gonzalez.

 The optimization of sperm freezing and storage program has an important impact on reducing breeding costs, improving reproductive efficiency, overcoming reproductive diseases, and protecting germplasm resources. In this paper, we have included two potential additives, sodium alginate (SA) and bovine serum albumin (BSA), which can effectively improve sperm motility after cryopreservation. This is of great significance for improving the quality of pig semen, improving reproductive ability and the development of modern pig breeding industry. Image by Jing Wang using Figdraw.

 In the past decade, flow cytometry has emerged as a crucial tool for assessing cellular viability in non-domestic animals, including non-human primates, marine life, and birds. Its application in sperm-quality assessments could revolutionize how we evaluate sperm concentration and viability, enhancing efficiency and reliability. This study validated the effectiveness of flow cytometry in assessing amphibian sperm, demonstrating its viability when compared with traditional, time-consuming methods. Such advancements highlight the potential of flow cytometry to significantly streamline conservation efforts for amphibians. Photograph by Ingrid Niesman, SDSU EM Facility.

 To clarify mechanisms of age-related infertility, we evaluated the decreased expression of CSF2, one of the most extensively studied embryokines, in aged bovine uteri compared to young ones. We observed suppressed CSF2 expression and increased myofibroblasts, which may contribute to fibrosis, in the uterine epithelium of older cows compared to young heifers. These findings suggest that decreased CSF2 alongside fibrosis may play crucial roles in age-related infertility, opening avenues for further research into potential therapies targeting fibrosis in reproductive health. Image by Hiroya Kadokawa.

 Exercise is suggested to have a beneficial role in improving the declining fecundity in humans, which is partly due to poor sperm parameters. Literature reports on the benefits of exercise for male reproductive function are, however, equivocal. This review summarises some of the reports and concludes that low-to-moderate intensity exercises, particularly those that do not increase testicular temperature or oxidative stress, are beneficial to male reproductive function. Image by authors

 Subfertile cows that get pregnant late in the breeding season are less productive. We found that fertile cows had more fat and muscle, greater circulating concentrations of metabolic hormones, healthy follicles with more granulosa cells and higher insulin-like growth factor 1 in the follicular fluid. Fertile cows had fewer circulating concentrations of progesterone but the sensitivity of the endometrium to progesterone and adiponectin was greater than in subfertile cows. Fertility was associated to the cow metabolism, that regulates uterine function to reduce embryo losses. Diagram adapted from Meikle et al. (2018).

 Plant extracts can be an alternative to treat some female infertility. Female fertility is a complex process regulated by hypothalamic–pituitary-ovarian unit involving both negative and positive feedback mechanisms. Because this hypothalamo–pituitary-ovarian axis is crucial in the regulation of female fertility, this review highlights mechanisms of action of various plant extracts on this axis. Diagram by J. Dupont using BioRender software.

 In this review, we explore the limitations on current genetic testing methods for embryos used in assisted reproductive technologies. We highlight the need for new solutions to address these clinical and technological challenges. Furthermore, we discuss a promising approach, metabolic imaging, which could potentially meet these clinical needs and improve the current issues faced by genetic testing for embryo selection. Image by Fabrizzio Horta.