Reproductive infertility treatment overview
Infertility treatment should be selected after etiologic evaluation, with therapy directed to the dominant cause (ovulatory dysfunction, tubal factor, endometriosis-associated infertility, male factor, or unexplained infertility) and escalation to assisted reproductive technology (ART) when appropriate [1]. Structured care pathways for fertility problems emphasize timely reassessment and referral to specialist fertility services when initial management fails [1].
Medication-based ovulation induction for anovulatory infertility (especially PCOS)
For infertile anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, letrozole is recommended as first-line pharmacologic ovulation induction [2]. For PCOS patients with anovulatory infertility and no other infertility factors, clomiphene citrate may be used instead of metformin for ovulation induction to improve ovulation and pregnancy outcomes [2]. For PCOS patients who fail first-line oral ovulation induction, gonadotropins are recommended as second-line pharmacologic therapy [2]. Exogenous gonadotropins can be used for ovulation induction in infertile anovulatory women when less complex methods fail or when oral agents are unlikely to achieve ovulation [3].
Assisted reproduction for unexplained infertility
For couples with unexplained infertility, an evidence-based sequence is recommended starting with ovarian stimulation plus intrauterine insemination (typically 3 or 4 cycles) before proceeding to in vitro fertilization (IVF) after unsuccessful treatment [4]. Natural cycle with IUI, clomiphene citrate with intercourse, aromatase inhibitors with intercourse, and multiple OS-IUI medication regimens are described as acceptable evidence-based options within the guideline treatment framework [4].
Treatment-directed management for endometriosis-associated infertility
For endometriosis-associated infertility, ART and surgical options are addressed within ESHRE endometriosis guidance, with decisions based on symptoms, age, prior surgery, other infertility factors, ovarian reserve, and an estimated endometriosis fertility index [7]. GnRH antagonist and GnRH agonist stimulation protocols for IVF/ICSI can be offered based on patient and clinician preferences, with no demonstrated difference in pregnancy or live birth rate between these approaches in the cited evidence base [7].
Tubal factor infertility and surgical roles
Tubal patency testing is emphasized as a prerequisite for appropriate therapy selection, with hysterosalpingography (HSG) described as a standard first-line test when reparative surgery is planned [5]. When ART is used as the default approach due to tubal disease, tubal surgery is positioned as an individualized strategy rather than routine therapy in the ART era [5].
Male factor infertility treatment options
Male infertility evaluation and treatment should address potentially correctable causes with medical or surgical therapy when applicable, and counseling regarding alternative pathways (e.g., donor sperm) when treatable etiologies are absent is emphasized in guideline recommendations [6]. The guideline addresses that benefits of supplements (e.g., antioxidants, vitamins) are of questionable clinical utility for treating male infertility [6].
ART treatment components and escalation to reduce multiples
Elective single-embryo transfer (eSET) is recommended to increase singleton live birth rates while avoiding multiple pregnancies, including in conjunction with aneuploidy testing where applicable [8]. Patients younger than 35 years should be strongly encouraged to receive single-embryo transfer regardless of embryo stage, within embryo number limits guidance [9]. Patients aged 41 to 42 years should plan to receive no more than 4 untested cleavage-stage embryos or 3 blastocysts, within embryo number limits guidance [9].
Practical escalation strategy across infertility phenotypes
Ovarian stimulation combined with IUI is recommended as an initial evidence-based treatment approach for unexplained infertility, with escalation to IVF after failure of initial cycles [4]. Oral ovulation induction is recommended as first-line for PCOS-related anovulatory infertility without other infertility factors, with stepwise escalation to gonadotropins after failure [2]. Etiology-directed management is recommended across tubal, endometriosis-associated, and male-factor infertility, with specialist-driven reassessment guiding transition to ART [1].
Common treatment pitfalls to avoid
Repeated ineffective cycles without addressing the dominant infertility cause are discouraged by guideline emphasis on directed evaluation and timely escalation to appropriate specialist care [1]. Routine reliance on supplement-based male infertility treatment is discouraged because clinical benefit is described as questionable in the guideline evidence summary [6].
Fertility treatment goals
Treatment should aim to achieve pregnancy while minimizing avoidable risks from infertility therapies, including avoidance of multiple gestation through use of elective single-embryo transfer and embryo number limits [8] [9].