Evolution of the WHO "Semen" processing manual from the first (1980) to the sixth edition (2021).

As stated clearly in all editions of the WHO Laboratory Manual for the Examination and Processing of Human Semen, the goal of the manual is to meet the growing needs for the standardization of semen analysis procedures. With constant advances in andrology and reproductive medicine and the advent of sophisticated assisted reproductive technologies for the treatment of infertility, the manual has been continuously updated to meet the need for new, evidence-based, validated tests to not only measure semen and sperm variables but also to provide a functional assessment of spermatozoa. The sixth edition of the WHO manual, launched in 2021, can be freely downloaded from the WHO website, with the hope of gaining wide acceptance and utilization as the essential source of the latest, evidence-based information for laboratory procedures required for the assessment of male reproductive function and health.

Distribution of semen examination results 2020 - A follow up of data collated for the WHO semen analysis manual 2010.

BACKGROUND: It is now 11 years since publication of the WHO 2010 guidelines for semen assessment values, and it is critical to determine whether they are still valid and/or whether they should be modified. OBJECTIVES: To utilise data published since 2010 and combine these with data used in the 2010 assessment to provide an updated and more comprehensive representation of the fertile man. This may be utilised to present an updated distribution of values for use by WHO in 2021. MATERIALS AND METHODS: Two specific analyses were performed namely, (1) Analysis 1: Examination of published data following publication of WHO 2010 [termed 2010-2020 data]. (2) Analysis 2: Examination of the data used to help formulate the 2010 distribution of values combined with the data from Analysis (1) [termed WHO 2020]. RESULTS: In total, data from more than 3500 subjects, from twelve countries and five continents were analysed. The 5th centile values for concentration, motility and morphology are: 16 × 106 /ml, 30% progressive motility [42% total motility] and 4% normal forms. DISCUSSION: This study presents substantial additional information to establish more comprehensive and globally applicable lower reference values for semen parameters for fertile men although they do not represent distinct limits between fertile and subfertile men. There are still data missing from many countries and, some geographical regions are not represented. Moreover, the number of subjects although significant is still relatively low (<4000). CONCLUSION: These distributions of values now include semen analysis providing a more global representation of the fertile man. Increasing the number of subjects provides robust information that is also more geographically representative.

Male Hormonal Contraception: Where Are We Now?

Hormonal male contraception clinical trials began in the 1970s. The method is based on the use of exogenous testosterone alone or in combination with a progestin to suppress the endogenous production of testosterone and spermatogenesis. Studies using testosterone alone showed that the method was very effective with few adverse effects. Addition of a progestin increases the rate and extent of suppression of spermatogenesis. Common adverse effects include acne, injection site pain, mood change including depression, and changes in libido that are usually mild and rarely lead to discontinuation. Current development includes long-acting injectables and transdermal gels and novel androgens that may have both androgenic and progestational activities. Surveys showed that over 50 % of men will accept a new male method and female partners will trust their partner to take oral "male pills." Partnership between government, nongovernment agencies, academia, and industry may generate adequate interest and collaboration to develop and market the first male hormonal contraception.

A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.

STUDY QUESTION: Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER: Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY: LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION: This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE: There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION: This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS: A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTERESTS: This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE: 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT: 10 January 2012.