Guideline for the prevention, diagnosis and treatment of infertility

What this guideline says

GMJ summary

This is the first comprehensive WHO guideline on infertility, addressing a global public health issue that affects approximately one in six people of reproductive age at some point in their lives. The guideline provides 35 evidence-based recommendations covering prevention (including information provision and tobacco cessation), diagnosis (of ovulatory dysfunction, tubal disease, uterine cavity disorders, and male factors), and treatment of female-factor, male-factor, and unexplained infertility.

Key diagnostic recommendations include using mid-luteal serum progesterone to confirm ovulation, hysterosalpingogram (HSG) or hysterosalpingo contrast sonography (HyCoSy) for tubal patency, and saline infusion sonohysterography (SIS) for uterine cavity assessment. For treatment, the guideline recommends letrozole over clomiphene citrate for PCOS-related infertility, surgical or radiological treatment for clinical varicocele, and a stepwise approach for unexplained infertility starting with expectant management, then stimulated intrauterine insemination (S-IUI), and finally IVF.

Developed using GRADE methodology with a multidisciplinary international panel, the guideline emphasizes that fertility care should be integrated into universal health coverage, accessible without stigma or discrimination, and provided with attention to equity, cost-effectiveness, and patient values. The recommendations use a public health perspective and are intended for adaptation to local contexts worldwide.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. For confirming ovulation in females with regular cycles: measure mid-luteal serum progesterone (approximately 7 days before expected menses); if no ovulation indicated, repeat measurement to minimize inaccurate diagnosis
2. For PCOS-related infertility: use letrozole as first-line over clomiphene citrate or metformin; where letrozole off-label use not permitted, use clomiphene citrate with metformin
3. For tubal patency assessment: use either HSG or HyCoSy based on local feasibility and trained provider availability
4. For uterine cavity assessment when disorder suspected: use SIS rather than 3D US, 2D US, or HSG
5. For males with abnormal semen parameters (outside WHO reference ranges): repeat semen analysis after minimum 11 weeks; if all parameters normal, do not repeat
6. For unexplained infertility: first-line is expectant management (3–6 months) rather than unstimulated IUI or ovarian stimulation; second-line is S-IUI with clomiphene citrate or letrozole (3–6 cycles); third-line is IVF without ICSI
7. For clinical varicocele in males: offer surgical or radiological treatment over expectant management; microscopic surgery preferred over other surgical approaches
8. Brief tobacco cessation advice (30 seconds to 3 minutes) should be routinely provided to all tobacco users in any health care setting, as smoking is associated with higher infertility risk, especially in women

Summary of recommendations and key guidance

Table extracted from the guideline

Source: World Health Organization, Guideline for the prevention, diagnosis and treatment of infertility. Reproduced in summary form.

From the guideline

Verbatim

“Approximately one in six people of reproductive age experience infertility at some stage in their lives.”

Editor’s perspective

Why this matters for Georgia and the region

Applicability

Georgia and the South Caucasus

Questions this guideline answers

Quick answers

Related on GMJ

Interconnected resources

GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.