BACKGROUND: As of 2019, high unmet contraceptive needs in low- and middle-income countries result in nearly half of all pregnancies being unintended. Additional male contraceptive options could help, but gaps remain in assessing demand for them. As the development of novel male contraceptives progresses, addressing these gaps would help inform policy and scientific direction.
OBJECTIVE: Measure consumer demand for novel male contraceptives and identify product attributes associated with men\'s preferences.
METHODS: A cross-sectional, probability-based-sample survey was conducted with 12,435 sexually active, fertile cisgender, heterosexual men aged 18-60 years, and 9,122 of their female partners in Bangladesh, Vietnam, Kenya, Nigeria, DR Congo, and Côte d\'Ivoire from May 2021 to October 2022. The survey was also conducted in the United States among 3,243 of these men in April 2022. A follow-up with 3,070 men in May 2023 assessed potential changes in demand after the Supreme Court\'s Dobbs v. Jackson Women\'s Health Organization decision. The surveys assessed contraceptive use, perceptions, and sociodemographic characteristics, and a discrete choice experiment evaluated preferences for 11 potential product attributes. Data from female partners in the six LMICs indicated their interest and trust in male partners\' contraceptive use.
RESULTS: On average, 61% of men showed interest in trying novel male contraceptives in their first year of availability, ranging from 39% and 49% (pre- and post-Dobbs) in the United States to 76% in Nigeria and Bangladesh. Form of administration and time of use drove men\'s product preferences. Female partners\' interest and trust in male contraceptive use were high across geographies.
CONCLUSIONS: This study reveals strong latent demand for novel male contraceptives, highlighting the potential for novel male methods to meet unmet needs, and female partners\' trust in men to use them.
CONCLUSIONS: High demand for novel male contraceptives among men and their partners exists, supporting investment in their development.

OBJECTIVE: To assess pregnancy risk following perfect use of the withdrawal method by quantification of sperm in pre-ejaculate.
METHODS: We conducted a pilot study of sperm and factors linked to its presence in pre-ejaculate samples among healthy, reproductive-age, withdrawal-experienced men. Participants provided up to three paired pre-ejaculate and ejaculate specimens in 72-hour intervals. We analyzed samples for volume, consistency, sperm concentration, count, and motility. We set clinical pregnancy risk as our primary outcome, defined as sperm concentration >1million/mL.
RESULTS: From 70 paired samples (N = 24 participants, median age: 27 years), we identified sperm in nine (12.9%) pre-ejaculate samples, from six (25.0%) participants. Only seven samples contained sperm in concentrations of significant clinical pregnancy risk. All ejaculatory specimens contained motile sperm in concentrations of significant pregnancy risk.
CONCLUSIONS: In this study of the pre-ejaculate of perfect-use withdrawal users, motile sperm were usually absent, or found inconsistently and in insufficient quantities to confer significant clinical pregnancy risk.
CONCLUSIONS: While correct and consistent withdrawal use is likely to be highly effective, given that motile sperm in concentrations >1 million/mL are usually absent or inconsistently present in pre-ejaculate, clinical trial data is lacking.

Novel male contraceptives have been in development for well over half a century, and despite a robust predicted global market for new methods, funding for research and development has been extremely limited. While the pharmaceutical industry previously supported male contraceptive research and development, industry partners are only spectators in the current space, awaiting a product that has been de-risked by the public sector before re-entering the field. Current male contraceptive development efforts are thus primarily funded by nonprofit, non-governmental, and government agencies who also act as the primary advocates for the field. Specific organizations include the International Consortium on Male Contraception, the Population Council, the Male Contraceptive Initiative, the World Health Organization, and the US National Institutes of Health. The funding provided by these public agencies, alongside their social and policy-based advocacy efforts such as market research, public education, and calls to action have kept the male contraceptive product development space afloat, resulting in a pipeline of potential products advancing towards market approval. However, as these products mature into more expensive clinical stages of development, they continue to face significant funding challenges, which many programs may not overcome. To fully realize the benefits of novel male contraceptive options, it is incumbent on philanthropic entities, impact investors, venture capital, and/or the pharmaceutical sector to provide significant and timely support for male contraceptive research and development.

BACKGROUND: Male contraception includes various methods designed to prevent pregnancy by focusing on the male\'s role in reproduction.
RESULTS: Behavioral methods, such as withdrawal and periodic abstinence, offer non-invasive alternatives that require self-control and precise timing to avoid depositing sperm in the female reproductive tract during fertile periods. However, these methods generally have low effectiveness and rely heavily on user adherence and experience. The male condom, a barrier method, provides both contraception and protection against sexually transmitted infections. Its effectiveness relies on correct and consistent use.
CONCLUSIONS: Access to comprehensive sexual education and medical counseling is essential to dispel the stigma surrounding contraceptive use and correct misconceptions, ensuring proper usage and ultimately contributing to better reproductive health outcomes.

BACKGROUND: Human spermatogenesis is a complex process that transforms spermatogonial stem cells through mitosis and meiosis to spermatozoa. Testosterone is the key regulator of the terminal stages of meiosis, adherence of spermatids to Sertoli cells, and spermiation. Follicle-stimulating hormone (FSH) may be required for early spermatogenesis and is important for maintaining normal spermatogenesis in men. Hormonal contraception suppresses FSH, luteinizing hormone, and intratesticular testosterone concentration, resulting in marked suppression of sperm output.
RESULTS: Clinical trials using testosterone alone or testosterone plus progestin demonstrate that sustained suppression of sperm concentration to ≤1 million/mL is sufficient to prevent pregnancy in the female partner. New agents that target spermatogenesis could use this as a target for contraceptive efficacy while others that block sperm function or transport may require a lower threshold. When sperm concentrations are suppressed to such low levels, measurement of sperm motility and morphology is technically difficult and unnecessary. With current data from fertile and infertile men, it is not possible to establish a lower limit of sperm motility or percent normal morphology that equates to the prevention of conception. New compounds that decrease sperm motility or alter sperm morphology may need to demonstrate a complete absence of sperm motility or altered morphology in all spermatozoa in the ejaculate. Sperm function tests may be useful depending on the mechanism of action of each new compound.
CONCLUSIONS: Monitoring of sperm surrogate markers to ensure effective contraception relies on laboratories experienced in semen analyses. The development of at-home tests to assess sperm parameters has progressed rapidly. Some tests have been assessed in clinical trials and approved by regulatory agencies for at-home use for fertility assessment. However, caution must be exercised in using these tests as many have not been rigorously validated against semen parameters measured in laboratories by trained technologists using standardized tests defined in the World Health Organization Semen Manual.

Spermatogenesis in mammalian testes is essential for male fertility, ensuring a continuous supply of mature sperm. The testicular microenvironment finely tunes this process, with retinoic acid, an active metabolite of vitamin A, serving a pivotal role. Retinoic acid is critical for various stages, including the differentiation of spermatogonia, meiosis in spermatogenic cells, and the production of mature spermatozoa. Vitamin A deficiency halts spermatogenesis, leading to the degeneration of numerous germ cells, a condition reversible with retinoic acid supplementation. Although retinoic acid can restore fertility in some males with reproductive disorders, it does not work universally. Furthermore, high doses may adversely affect reproduction. The inconsistent outcomes of retinoid treatments in addressing infertility are linked to the incomplete understanding of the molecular mechanisms through which retinoid signaling governs spermatogenesis. In addition to the treatment of male reproductive disorders, the role of retinoic acid in spermatogenesis also provides new ideas for the development of male non-hormone contraceptives. This paper will explore three facets: the synthesis and breakdown of retinoic acid in the testes, its role in spermatogenesis, and its application in male reproduction. Our discussion aims to provide a comprehensive reference for studying the regulatory effects of retinoic acid signaling on spermatogenesis and offer insights into its use in treating male reproductive issues.

The World Health Organization has been involved in male contraceptive development for over 50 years. In line with its functions and mandate, World Health Organization works with diverse stakeholders to support research, develop norms and standards, engage member states, facilitate prequalification, introduction and scale up, measurement, and tracking of contraceptives. World Health Organization has a key role in galvanizing global efforts to ensure universal access to contraception services irrespective of income group. Regarding male contraceptive development, World Health Organization has provided technical leadership, supported early research, created and supported research centers, built research capacity in various countries, and standardized semen analysis procedures. In this paper, a detailed description is provided with examples across the various stages of male contraceptive development. Limited funding to World Health Organization is a key challenge.

The last few decades have brought contraception to the forefront of research, with great strides made in effectively targeting and optimizing the physiology, pharmacology, and delivery processes that prevent pregnancy. However, these advances still predominantly target female contraceptives for the prevention of contraception, whereas targeting the male sex has lagged far behind. This has led to a marked deficiency in safe and effective male contraceptive agents, resulting in a heavy dependence on female contraceptives to prevent unwanted and unplanned pregnancies. Current research in the veterinary field and in rodents highlights several promising avenues whereby novel, safe, and effective male contraceptive alternatives are being developed-with an emphasis on reduced side effects and reversibility potential. This review aims to discuss current and novel male contraceptives (both human and veterinary formulations) while highlighting their efficacy, advantages, and disadvantages.

BACKGROUND: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning.
OBJECTIVE: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel.
CONCLUSIONS: Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product\'s efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy.
CONCLUSIONS: There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

BACKGROUND: Currently, approximately half of all pregnancies worldwide are unintended. Contraceptive use significantly reduces the risk of unintended pregnancy; however, options for men are particularly limited. Consequently, efforts are underway to develop novel, safe, and effective male contraceptives.
RESULTS: This review discusses research into emerging male contraceptive methods that either inhibit sperm production or impair sperm function. It focuses on those in the preclinical or early clinical stages of development.