Optimal Diagnosis and Medical Treatment of Male Infertility

 

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For most, conceiving a child is straightforward and does not involve special planning or intervention. Unfortunately, 15 to 20% of couples will experience undesired delays in conception[1] [2] and seek medical advice for ways to improve fertility. Male infertility is often a frustrating problem, because it is a multifactorial disorder for which an identifiable cause cannot be found in a significant percentage of cases.[3] Unfortunately, for those diagnosed with male-factor infertility, there is a paucity of tried and true treatments and even fewer level-1 evidence-based guidelines. This publication presents a multimodal approach to improve male fertility, by optimizing hormonal balance, minimizing DNA/genetic damage, and utilizing holistic options to minimize stress.

Advancing techniques and continuously improving success rates with in vitro and in vivo technologies have allowed reproductive specialists to offer fertility to those with significant struggles. By using the multimodal approach described here, I am hopeful that male-factor fertility can be optimized to the point that less invasive reproductive interventions—including restoration of the natural conception option—can be considered.

For the past 5 years, I have had the privilege of working with the Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Reproductive Medicine Network (RMN). The RMN is a multicenter clinical trial network tasked with formulating and conducting clinical trials focused on improving reproductive outcomes in subfertile populations. This particular iteration of the network was unique in that each participating site was required to have a coinvestigator with expertise in male-factor infertility. It is my pleasure to introduce you to a remarkable ensemble of researchers with whom I have had the honor to work, either at the RMN or the Upstate University Hospital. Herein, they present suggestions for nonsurgical options to improve male-factor fertility. My goal is that this seminar's publication would assist all of us who treat infertile men by providing multiple suggestions for ways to medically optimize male fertility. I wish that the suggestions you are about to read were all clearly defined by prospective studies and supported by level-1 evidence. Unfortunately, for most cases, this has yet to occur. Nonetheless, I trust that the content provided here will outline a multimodal approach to treating men with infertility and provide a synergistic improvement in male fertility. Moreover, this information may act as a catalyst for future collaborative research opportunities, which will result in more clearly defined guidelines for treating male infertility.

Current and novel medical therapies for male infertility are conveniently broken down into four sections:

1. It starts with an overview of the hypothalamus–pituitary–gonadal axis.

   • Male Reproductive Endocrinology: When to Replace Gonadotropins

     I was honored to have Dr. Peter J. Snyder's input regarding this review of one of the more treatable forms of male infertility: hypogonadotropic hypogonadism. Current options for gonadotropin replacement (Table 3) and which patients would be most likely to respond (Table 4) are discussed.

2. The next two articles review off-label use of medications for optimizing hypothalamus–pituitary–gonadal function.

   • Clomiphene Citrate in the Management of Male Infertility

     Doctors Lauren Roth, Amanda Ryan, and Randall Meacham outline the specific clinical scenarios whereby clomiphene citrate may be appropriate for the management of male infertility.

   • Big Enough for an Aromatase Inhibitor? How Adiposity Affects Male Fertility

     Doctors Sahar Stephens and Alex Polotsky explore the association between obesity and subfecundity. They review studies that have shown promising findings regarding the use of aromatase inhibitors for the treatment of hypogonadotropic hypogonadism in obese and subfertile men with abnormal hormonal profiles.

3. The next three articles explore genetic topics.

   • Risks of Reproducing with a Genetic Disorder

     Melissa Byler, MS, and Dr. Robert Lebel outline the most common causes for the 15% of infertile men with a genetic disorder. By knowing what specific genetic risks exist for the offspring of men with these particular disorders, preimplantation genetic diagnosis can be used to detect problems, and thereby minimize the risk of perpetuating a genetic disorder.

   • Detecting and Minimizing Sperm DNA Damage

     Doctors Yachao Zhang and Kazim Chohan explain how sperm DNA fragmentation diminish the chance of success in assisted pregnancies, while DNA damage can impair fertilization, disrupt embryonic development, and increase miscarriage rates. Suggestions are made for minimizing sperm DNA damage.

   • Optimizing Fertility Preservation for Pre- and Post-pubertal Males with Cancer

     Doctors Jonathan Wang, Charles Muller, and Kathleen Lin outline the risk of azoospermia in males treated with various cancer regimens (Table 1). Fortunately, recovery of spermatogenesis is sometimes possible in men previously treated with cytotoxins, without evidence for an increase in abnormalities among the offspring. Moreover, there does not appear to be an increase in sporadic juvenile malignancies in the progeny of cancer survivors.

4. The last three articles explore nonmedical (holistic) approaches to improving male fertility.

   • Avoiding Toxins Including Spermatotoxic Medications

     Doctors Gillian Stearns and Paul J. Turek reviewed 35 years of the English literature to examine drugs, medications, and other exposures that have been linked to altered semen quality and male fertility.

   • Nutrient Supplementation: Improving Male Fertility Fourfold

     Doctors Cesar Mora-Esteves and David Shin outline how oxidative stressors can impair spermatogenesis. Unfortunately, the effectiveness of various antioxidants is variable. Nonetheless, a recent Cochrane review determined that men taking antioxidants had a statistically significant increase in both live birth rates and pregnancy rates. For those undergoing assisted reproduction, the odds ratio that antioxidant use would improve pregnancy rates was 4.18, with a 4.85-fold improvement in live birth rate also noted.

   • Eastern Medicine Approaches to Male Infertility

     In this article, doctors Min Hu, Yuehui Zhang, Hongli Ma, Ernest H. Y. Ng, and Xiao-Ke Wu describe the clinical effectiveness of the following eastern medicine approaches to male fertility: acupuncture, Chinese herbal medicine, massage, yoga, tai chi, and qi gong.

• References

• 1 World Health Organization. Programme of Maternal and Child Health and Family Planning Unit. Infertility: a tabulation of available data on prevalence of primary and secondary infertility. Geneva: World Health Organization; 1991: 1-79
  Google Scholar
• 2 Philippov OS, Radionchenko AA, Bolotova VP, Voronovskaya NI, Potemkina TV. Estimation of the prevalence and causes of infertility in western Siberia. Bull World Health Organ 1998; 76 (2) 183-187
  PubMedGoogle Scholar
• 3 Bonanomi M, Lucente G, Silvestrini B. Male fertility: core chemical structure in pharmacological research. Contraception 2002; 65 (4) 317-320
  CrossrefPubMedGoogle Scholar