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.
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.
Eliran Mor MDTo 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.
Resistin belongs to adipokines – the group of hormones secreted mainly by the adipose tissue that can regulate not only energy homeostasis but also reproductive functions. We determined the presence of resistin in the uterus and its impact on the uterine steroidogenesis of pigs, an important farm animal. The obtained results suggest that resistin may interconnect metabolism and reproduction, and in the long-term perspective, these results may help improve farm animal breeding efficiency. Image by the authors
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.