Portal de Periódicos da CAPES

Don’t forget the father

2022; Elsevier BV; Volume: 117; Issue: 5 Linguagem: Inglês

10.1016/j.fertnstert.2022.03.012

1556-5653

Michael L. Eisenberg, Christopher L. R. Barratt, Christopher J. De Jonge,

Sperm and Testicular Function

Although the father contributes half the DNA to the child, evaluation of the man before conception sometimes is overlooked. For example, for couples seeking help with infertility, the male evaluation is bypassed 20%–25% of the time in contradiction to societal guidelines (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 2Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.Fertil Steril. 2021; 115: 62-69Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Indeed, a male evaluation can identify important etiologies which can lead to treatments to improve semen quality and reproductive outcomes (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 2Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.Fertil Steril. 2021; 115: 62-69Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). In addition, to infertile couples, there also are data to suggest that preconception paternal health is an important factor for all births. Studies have demonstrated associations between a father's health and semen quality, time to pregnancy, pregnancy loss, and preterm birth (3Salonia A. Matloob R. Gallina A. Abdollah F. Sacca A. Briganti A. et al.Are infertile men less healthy than fertile men? Results of a prospective case-control survey.Eur Urol. 2009; 56: 1025-1031Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). Moreover, the risk of maternal preeclampsia and gestational diabetes increases with the number of paternal comorbidities. Thus, evaluating and counseling a prospective father could improve a couple's ability to conceive, and have a healthy, uncomplicated pregnancy, and a term child.Importantly, several demographic shifts are occurring in parents. Recent data suggest fewer than half of new mothers have favorable cardiometabolic health. Similarly, studies also have demonstrated that paternal health has declined over time. In addition, parental age continues to increase. Over the past 40 years, the average father has become 3.5 years older in the United States. Today, approximately 1% of all births in the United States are conceived by fathers older than 50 years. Again, studies have demonstrated adverse associations with the health of the pregnancy and child.Although the mother undoubtedly is key to conception and successful gestation, the father exerts an undeniable role. Women have regular reminders of their own fertility, but before conception a man generally is unaware of his reproductive potential without explicit evaluation. However, more attention to male reproductive health (MRH) may help a man, his partner, and society. As one examines male reproduction, there are important points about the current state of affairs and opportunities for improvement.A consistent challenge in improving research quality and quantity in MRH is the paucity of research funds. Remarkably, a recent analysis from the United Kingdom and United States showed that <1% of the government research funding was awarded to projects involving MRH (4Gumerova E, De Jonge CJ, Barratt CLR. Research Funding for male reproductive health and infertility in the UK and USA [2016–2019]. Hum Fertil. In press.Google Scholar). This is far from concomitant with the burden and impact that MRH has on society. It is incumbent upon us, as professionals, to rectify this disparity urgently by presenting compelling arguments to policy makers to place MRH at the vanguard of the funding portfolio.Another area for improvement to help the father, his partner, his family, and society is to reduce barriers in access to male infertility care. Infertility is a disease, and it should be covered by insurance like other diseases (5Dupree J.M. Insurance coverage of male infertility: what should the standard be?.Transl Androl Urol. 2018; 7: S310-S316Crossref PubMed Scopus (10) Google Scholar). Presently, many insurance companies do not provide coverage for male infertility care, and only a handful of states mandate coverage. Thus, for many men and their partners, infertility care costs present a financial and health care-seeking barrier. Data from the National Survey for Family Growth demonstrate that equity in access to male infertility services is limited by barriers of insurance, education level, and household income.The American Urological Association/American Society for Reproductive Medicine guidelines for the evaluation of male infertility provides direction for another area for improvement in helping the (putative) father and his partner. After an abnormal semen analysis, the male should be evaluated by a male reproductive expert (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Often when men make a visit for an infertility investigation, they are seen by a nonurologist. This may be due to lack of referral or lack of engagement/participation of men who may not accompany their partner to fertility visits. Even at a tertiary care center, where one might anticipate a high reproductive urologist visit rate, a relatively high percentage of men (40%) receive care from a generalist or female reproductive expert (i.e. reproductive endocrinologist [REI]). Consequently, these men may have incomplete or inaccurate understanding of how their results relate to achieving pregnancy with their partner. It is important to acknowledge that men often do not seek health care actively except for acute conditions. Thus, the female partner is responsible mostly for initiating an infertility investigation, and that typically takes place through her obstetrician or REI. Reassuring for the couple is that most of REIs are being effective "gatekeepers" by reinforcing American Urological Association/American Society for Reproductive Medicine guidelines for referring male patients to a male reproductive expert for evaluation.Another topic for improvement is policy and practice reform in the early education of future fathers. Traditionally, teenage boys receive "sex" education that rightly focuses on contraception and prevention of sexually transmitted infections. We know today that more information must be added to the conversation for these "future fathers". As has been presented herein, there is a connection between somatic and reproductive health. Males progressing from late teens to mid-to-late twenties often engage in behaviors that can negatively impact health and consequently reproductive health, such as tobacco and/or recreational drug use, androgenic steroids, and poor nutrition. This demographic also tends to disappear from regular health care visits. By educating teen boys and young adult men about developing healthy strategies, a shift may occur from corrective or curative care to preventive health care. Importantly, engagement of boys and men in prevention and management of fertility through healthy habits and lifestyles is necessary for their health and their relationship to partners and offspring, and contributes to achieving gender equality in reproduction and beyond.Just as fertility pursuits require the participation of men and women, so does engagement in male contraception. Indeed, men and women are now more willing to be engaged in male contraception and there has been development of global strategic funding from the Bill and Melinda Gates Foundation (www.gatesfoundation.org) and generation of organizations, such as Male Contraceptive Initiative (www.malecontraceptive.org). These have fostered awareness and significantly boosted research in this area. At the same time, there is continued progress in the search for effective hormonal contraception regimens (e.g., different vehicles/formulations of administration). Furthermore, there is substantive progress in basic research identifying targets and mechanism of operation of key players and pathways in spermatogenesis, sperm maturation in the epididymis, and in the mature spermatozoon (www.malecontraceptive.org/nhrmc-database.html). These, coupled with the rapid progress in identifying formulations that can be used in the female reproductive tract adversely affecting sperm function mean that we are now more confident of realizing the promise of male nonhormonal contraceptive approaches than we have been for a long time.A final important aspect of male fertility is the close association with general health. Indeed, semen quality and time to pregnancy are associated with a man's overall health. Although prior cancer treatments are known to impair semen quality, other health ailments also may have a role. Investigators have used a variety of health metrics (e.g., Charlson Comorbidity Index, Metabolic Syndrome, common chronic diseases, and so forth) and have demonstrated consistently that as health declines so does semen quality (3Salonia A. Matloob R. Gallina A. Abdollah F. Sacca A. Briganti A. et al.Are infertile men less healthy than fertile men? Results of a prospective case-control survey.Eur Urol. 2009; 56: 1025-1031Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar).In addition, semen quality also may be a harbinger of future health. One classic example of this has been that infertile men have a higher risk for testis cancer. While it is simple to conceive a common etiology between impaired spermatogenesis and germ cell carcinogenesis, investigators also have linked male fertility to other cancers (e.g., prostate, lymphoma, and breast). Moreover, there is a dose-response relationship so that men with worse semen quality seem to have the highest risk of cancer. Investigators have hypothesized a genetic, developmental, environmental, or psychosocial link to explain the relationship between health and fertility.Male infertility is associated with other health outcomes, including heart disease, diabetes, autoimmune disease, hospitalizations, and even mortality. Thus, in addition to reproductive goals, a male fertility evaluation may also identify serious medical problems and present an opportunity for a realignment of a man's health trajectory.As with many aspects in modern culture, celebrities highlighting the importance of MRH can bring important attention to the cause. Mark Zuckerberg announced, in a Facebook post, the struggles he and his wife had with recurrent miscarriage. Jimmy Fallon discussed his own 5-year struggle with infertility. Hugh Jackman revealed the pain of infertility and failed in vitro fertilization cycles before finally becoming a parent with his wife. In addition, recognizing that the father's contribution does not end at conception or even delivery, several high profile fathers have publicly taken paternity leave, such as Zuckerberg (2 months), Alexis Ohanian (16 weeks), and Parag Agrawal (several weeks just months after taking over as the CEO of Twitter). Importantly, such opportunities are not available to all fathers in society. Nevertheless, there is growing attention to male reproduction. However, while improvements in MRH are occurring, there remains work to do to educate society on the importance of male fertility for this and future generations. Although the father contributes half the DNA to the child, evaluation of the man before conception sometimes is overlooked. For example, for couples seeking help with infertility, the male evaluation is bypassed 20%–25% of the time in contradiction to societal guidelines (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 2Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.Fertil Steril. 2021; 115: 62-69Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Indeed, a male evaluation can identify important etiologies which can lead to treatments to improve semen quality and reproductive outcomes (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 2Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.Fertil Steril. 2021; 115: 62-69Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). In addition, to infertile couples, there also are data to suggest that preconception paternal health is an important factor for all births. Studies have demonstrated associations between a father's health and semen quality, time to pregnancy, pregnancy loss, and preterm birth (3Salonia A. Matloob R. Gallina A. Abdollah F. Sacca A. Briganti A. et al.Are infertile men less healthy than fertile men? Results of a prospective case-control survey.Eur Urol. 2009; 56: 1025-1031Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). Moreover, the risk of maternal preeclampsia and gestational diabetes increases with the number of paternal comorbidities. Thus, evaluating and counseling a prospective father could improve a couple's ability to conceive, and have a healthy, uncomplicated pregnancy, and a term child. Importantly, several demographic shifts are occurring in parents. Recent data suggest fewer than half of new mothers have favorable cardiometabolic health. Similarly, studies also have demonstrated that paternal health has declined over time. In addition, parental age continues to increase. Over the past 40 years, the average father has become 3.5 years older in the United States. Today, approximately 1% of all births in the United States are conceived by fathers older than 50 years. Again, studies have demonstrated adverse associations with the health of the pregnancy and child. Although the mother undoubtedly is key to conception and successful gestation, the father exerts an undeniable role. Women have regular reminders of their own fertility, but before conception a man generally is unaware of his reproductive potential without explicit evaluation. However, more attention to male reproductive health (MRH) may help a man, his partner, and society. As one examines male reproduction, there are important points about the current state of affairs and opportunities for improvement. A consistent challenge in improving research quality and quantity in MRH is the paucity of research funds. Remarkably, a recent analysis from the United Kingdom and United States showed that <1% of the government research funding was awarded to projects involving MRH (4Gumerova E, De Jonge CJ, Barratt CLR. Research Funding for male reproductive health and infertility in the UK and USA [2016–2019]. Hum Fertil. In press.Google Scholar). This is far from concomitant with the burden and impact that MRH has on society. It is incumbent upon us, as professionals, to rectify this disparity urgently by presenting compelling arguments to policy makers to place MRH at the vanguard of the funding portfolio. Another area for improvement to help the father, his partner, his family, and society is to reduce barriers in access to male infertility care. Infertility is a disease, and it should be covered by insurance like other diseases (5Dupree J.M. Insurance coverage of male infertility: what should the standard be?.Transl Androl Urol. 2018; 7: S310-S316Crossref PubMed Scopus (10) Google Scholar). Presently, many insurance companies do not provide coverage for male infertility care, and only a handful of states mandate coverage. Thus, for many men and their partners, infertility care costs present a financial and health care-seeking barrier. Data from the National Survey for Family Growth demonstrate that equity in access to male infertility services is limited by barriers of insurance, education level, and household income. The American Urological Association/American Society for Reproductive Medicine guidelines for the evaluation of male infertility provides direction for another area for improvement in helping the (putative) father and his partner. After an abnormal semen analysis, the male should be evaluated by a male reproductive expert (1Schlegel P.N. Sigman M. Collura B. De Jonge C.J. Eisenberg M.L. Lamb D.J. et al.Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.Fertil Steril. 2021; 115: 54-61Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Often when men make a visit for an infertility investigation, they are seen by a nonurologist. This may be due to lack of referral or lack of engagement/participation of men who may not accompany their partner to fertility visits. Even at a tertiary care center, where one might anticipate a high reproductive urologist visit rate, a relatively high percentage of men (40%) receive care from a generalist or female reproductive expert (i.e. reproductive endocrinologist [REI]). Consequently, these men may have incomplete or inaccurate understanding of how their results relate to achieving pregnancy with their partner. It is important to acknowledge that men often do not seek health care actively except for acute conditions. Thus, the female partner is responsible mostly for initiating an infertility investigation, and that typically takes place through her obstetrician or REI. Reassuring for the couple is that most of REIs are being effective "gatekeepers" by reinforcing American Urological Association/American Society for Reproductive Medicine guidelines for referring male patients to a male reproductive expert for evaluation. Another topic for improvement is policy and practice reform in the early education of future fathers. Traditionally, teenage boys receive "sex" education that rightly focuses on contraception and prevention of sexually transmitted infections. We know today that more information must be added to the conversation for these "future fathers". As has been presented herein, there is a connection between somatic and reproductive health. Males progressing from late teens to mid-to-late twenties often engage in behaviors that can negatively impact health and consequently reproductive health, such as tobacco and/or recreational drug use, androgenic steroids, and poor nutrition. This demographic also tends to disappear from regular health care visits. By educating teen boys and young adult men about developing healthy strategies, a shift may occur from corrective or curative care to preventive health care. Importantly, engagement of boys and men in prevention and management of fertility through healthy habits and lifestyles is necessary for their health and their relationship to partners and offspring, and contributes to achieving gender equality in reproduction and beyond. Just as fertility pursuits require the participation of men and women, so does engagement in male contraception. Indeed, men and women are now more willing to be engaged in male contraception and there has been development of global strategic funding from the Bill and Melinda Gates Foundation (www.gatesfoundation.org) and generation of organizations, such as Male Contraceptive Initiative (www.malecontraceptive.org). These have fostered awareness and significantly boosted research in this area. At the same time, there is continued progress in the search for effective hormonal contraception regimens (e.g., different vehicles/formulations of administration). Furthermore, there is substantive progress in basic research identifying targets and mechanism of operation of key players and pathways in spermatogenesis, sperm maturation in the epididymis, and in the mature spermatozoon (www.malecontraceptive.org/nhrmc-database.html). These, coupled with the rapid progress in identifying formulations that can be used in the female reproductive tract adversely affecting sperm function mean that we are now more confident of realizing the promise of male nonhormonal contraceptive approaches than we have been for a long time. A final important aspect of male fertility is the close association with general health. Indeed, semen quality and time to pregnancy are associated with a man's overall health. Although prior cancer treatments are known to impair semen quality, other health ailments also may have a role. Investigators have used a variety of health metrics (e.g., Charlson Comorbidity Index, Metabolic Syndrome, common chronic diseases, and so forth) and have demonstrated consistently that as health declines so does semen quality (3Salonia A. Matloob R. Gallina A. Abdollah F. Sacca A. Briganti A. et al.Are infertile men less healthy than fertile men? Results of a prospective case-control survey.Eur Urol. 2009; 56: 1025-1031Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar). In addition, semen quality also may be a harbinger of future health. One classic example of this has been that infertile men have a higher risk for testis cancer. While it is simple to conceive a common etiology between impaired spermatogenesis and germ cell carcinogenesis, investigators also have linked male fertility to other cancers (e.g., prostate, lymphoma, and breast). Moreover, there is a dose-response relationship so that men with worse semen quality seem to have the highest risk of cancer. Investigators have hypothesized a genetic, developmental, environmental, or psychosocial link to explain the relationship between health and fertility. Male infertility is associated with other health outcomes, including heart disease, diabetes, autoimmune disease, hospitalizations, and even mortality. Thus, in addition to reproductive goals, a male fertility evaluation may also identify serious medical problems and present an opportunity for a realignment of a man's health trajectory. As with many aspects in modern culture, celebrities highlighting the importance of MRH can bring important attention to the cause. Mark Zuckerberg announced, in a Facebook post, the struggles he and his wife had with recurrent miscarriage. Jimmy Fallon discussed his own 5-year struggle with infertility. Hugh Jackman revealed the pain of infertility and failed in vitro fertilization cycles before finally becoming a parent with his wife. In addition, recognizing that the father's contribution does not end at conception or even delivery, several high profile fathers have publicly taken paternity leave, such as Zuckerberg (2 months), Alexis Ohanian (16 weeks), and Parag Agrawal (several weeks just months after taking over as the CEO of Twitter). Importantly, such opportunities are not available to all fathers in society. Nevertheless, there is growing attention to male reproduction. However, while improvements in MRH are occurring, there remains work to do to educate society on the importance of male fertility for this and future generations.