Secondary Infertility

Secondary Infertility - how common is it, what are the main reasons it occurs and how is it managed clinically?

Introduction

Secondary infertility is clinically defined as the inability of a couple to conceive after a previous successful pregnancy. When looked at a global picture, the trends vary quite significantly geographically. This difference in variance has remained relatively stable between 1990 and 2010, with regional fluctuations. Data suggest that the global burden of secondary infertility often exceeds that of primary infertility, particularly in regions such as Sub-Saharan Africa (where most of the countries are classified as low-to-middle income countries - often abbreviated as LMIC’s). Despite this substantial prevalence (existing cases), the condition is often underreported and/or lacks systematic clinical documentation.

As mentioned previously,

Sub-Saharan Africa has the highest reported prevalence of secondary infertility globally.

Estimated prevalence:

• 15–30% of couples in some communities
• Higher than primary infertility in many countries

Countries with particularly high burdens include:

• Nigeria
• Ghana
• Cameroon
• Uganda
• Kenya
• Ethiopia
• South Africa (particularly among women with untreated pelvic inflammatory disease and HIV)

Beyond immediate clinical metrics, the long-term reproductive health implications patients going through secondary infertility can potentially cause lifelong psychological impacts stemming from the trauma of prolonged subfertility. Integrating supportive counselling and cognitive-behavioural interventions is essential to mitigate these adverse psychosocial outcomes and foster resilience throughout the extended examination and treatment trajectory.

Epidemiological Trends (The spread of Disease)

As noted previously, secondary infertility has significant differences in number of cases across many countries, especially pooled in number of cases across African nations, such as those observed between East and North Africa. Researchers describe how the variations are often exacerbated by issues such as: inconsistencies in health survey methodology, where secondary infertility could account for as much as 33.2% of cases in certain urban centres, which when compared to global averages, is skewed.

Another well documented reason for the prevalence of secondary infertility is linked to maternal age. With increased maternal age, ovarian reserve becomes depleted which significantly impacts on subsequent conception. Sometimes, complex physiological events experienced in prior obstetric events—particularly caesarean sections—often contribute to complications such as uterine scarring and pelvic adhesions.

Physical Root Factors

From a physical perspective, tubal and uterine pathologies can manifest as pelvic inflammatory disease or post-surgical adhesions, which in turn can physically obstruct gamete transport and embryo implantation.

Repeated pelvic inflammatory disease remains a primary driver of tubal factor infertility, as these infections can lead to tubal occlusion and impaired ciliary function within the ovarian tubes. Uterine fibroids and intrauterine adhesions serves as a mechanical barrier to successful implantation, often arising as long-term complications of obstetric events for females. In addition, ovulatory dysfunction has been shown to be a critical factor.

As far as infections are concerned, such as chlamydia and gonorrhoea can often result in irreversible tubal damage, while procedures like dilation and curettage (D&C), may lead to what is called Asherman’s syndrome (scar tissue inside the uterus) or similar intrauterine diseases such as fibroids. Furthermore, ovulatory dysfunction frequently arises from endocrine irregularities, such as polycystic ovary syndrome or hyperprolactinemia, which may present or exacerbate during the postpartum interval.

In secondary infertility, the male factor should never be ignored. Frequent male infections, such as urogenital infections, can impair sperm quality and transport over time. Infectious testicular insults could cause obstructive azoospermia or secondary deficits in spermatogenesis which can account for a significant portion of couples' inability to conceive.

Furthermore, the multifactorial nature of ovulatory dysfunction often involves polycystic ovary syndrome, which, alongside secondary metabolic dysregulation, frequently impairs follicular development.

Male Factor Infertility

Clinical investigation for male factors includes analyses of the semen, looking for number and quality of the sperm. Sperm should be examined over time, to also assess for possible declining sperm concentration and motility. Another examination, should include physical exam of the male testicles. If varicoceles (enlargement of the veins within the scrotum) - similar to varicose veins in the legs - are identified, this factor is one of the most frequent reversible aetiology of male secondary infertility.

On-going epidemiological surveillance has shown that declining sperm concentration and motility are increasingly linked to systemic environmental exposures, including endocrine-disrupting chemicals such as phthalates and bisphenol A. It has been noted that these substances, alongside other chronic lifestyle-related stressors, contribute to the growing global trend of diminished semen parameters in previously fertile men.

Additionally, chronic tobacco consumption and occupational exposure to ionizing radiation are recognized as significant determinants that negatively impact semen integrity, potentially leading to persistent reproductive challenges.

Diagnostic Assessment

When talking to your healthcare provider, insist that a comprehensive diagnostic evaluation is done, including a structured clinical history, past obstetric complications, surgical procedures, and exposure to possible reproductive toxins. Clinicians should systematically document the duration of secondary infertility, timing of previous obstetric outcomes, and any history of pelvic inflammatory disease or sexually transmitted infections.

Subsequently, clinicians must execute a panel of hormonal assays, serum studies for ovarian reserve assessment, as well as follicle-stimulating hormone and oestradiol on cycle day 2 to evaluate hypothalamic-pituitary-ovarian axis integrity.

Additionally, clinicians should perform an antral follicle count via transvaginal ultrasound, as these assessments serve as critical second-level investigations for couples where male semen parameters remain within normal ranges. The uterine cavity and tubal patency should be examined to exclude structural impediments to conception. Furthermore, for cases involving suspected pelvic adhesions or endometriosis, laparoscopic visualization remains the diagnostic gold standard, offering both definitive anatomical confirmation and potential therapeutic intervention.

Management Principles

Management strategies for secondary infertility prioritize individualized therapeutic pathways, tailoring interventions such as ovulation induction, intrauterine insemination, or advanced reproductive technologies like IVF based on specific physiological findings and the couple's reproductive history.

These tailored protocols incorporate consistent hormonal monitoring and ultrasound surveillance to refine medication dosages, thereby optimizing endometrial receptivity and follicular maturation.

Complementary to clinical interventions, structured lifestyle modifications—such as weight optimization, smoking cessation, and targeted nutritional adjustments—serve as essential first-line strategies to improve natural conception rates, particularly in patients with metabolic or ovulatory disturbances. Beyond physiological management, the integration of comprehensive psychosocial support is paramount to address the profound stress, guilt, and emotional strain inherent in navigating secondary infertility.

Assisted Reproductive Technology

Success rates for in vitro fertilization are heavily dependent on patient selection criteria, particularly in cases where diminished ovarian reserve or advanced maternal age necessitates the use of donor oocytes to achieve viable pregnancies.

Clinicians must prioritize candidates demonstrating optimal antral follicle counts and favourable uterine morphology to maximize the probability of a live birth. While overall IVF success remains subject to age-related decline, protocols for secondary infertility patients often achieve higher implantation rates when intrauterine pathologies, such as polyps or adhesions, are surgically corrected prior to embryo transfer . In these instances, rigorous pre-treatment evaluation ensures that structural impediments are resolved, thereby significantly enhancing the overall efficacy of assisted reproductive cycles.

Clinical Prognosis

Treatment outcomes for secondary infertility are multifactorial, significantly influenced by female age, the duration of subfertility, and the specific underlying pathology. The resolution of anatomical obstructions and the management of male factor contributions have markedly improved clinical prognosis, even for couples previously considered poor candidates for conception.

When clinicians also account for lifestyle variables, as behaviours such as alcohol consumption, caffeine intake, and exposure to toxic bisphenols, success rates improve.

Key Take-Home Message

The highest prevalence of secondary infertility is found in Sub-Saharan Africa, where reproductive tract infections and preventable obstetric complications remain major causes. As countries undergo demographic and lifestyle transitions, the pattern of secondary infertility is changing, with age-related infertility, obesity, endometriosis, and metabolic disorders becoming increasingly important worldwide. This highlights the need for integrated reproductive health services that combine infection prevention, safe maternity care, chronic disease management, and equitable access to fertility evaluation and treatment.

The Situation in South Africa

South Africa experiences a dual burden of secondary infertility.

In public sector populations, common causes include:

• HIV-associated reproductive tract disease
• Untreated STIs
• Pelvic inflammatory disease
• Tubal factor infertility
• Postpartum sepsis
• Post-aborted infections

In the private sector, increasing contributors include:

• Delayed childbearing
• Obesity
• PCOS
• Endometriosis
• Male infertility

Significant inequalities in access to fertility assessment and assisted reproductive technologies persist between the public and private sectors.

References include, but not limited:

Abebe, A., Afework, M., & Abaynew, Y. (2020). Primary and secondary infertility in Africa: systematic review with meta-analysis. Fertility Research and Practice, 6(1), 20–20. https://doi.org/10.1186/s40738-020-00090-3

Abtew, K. M. (2024). The Magnitude of Secondary Infertility and Associated Factors among Married Women Attending Outpatient Clinics, in Addis Ababa, Ethiopia. In Research Square. https://doi.org/10.21203/rs.3.rs-5116633/v1

Akhtar, S., Nasreen, R., Bibi, H., Khan, A. A., Baig, A. A., & Riffat, N. (2022). Reproductive Features of Patients with Secondary Infertility. 16(10), 111–112. https://doi.org/10.53350/pjmhs221610111

Davis, C. H., Hall, M. N., Kaufmann, L., & Danis, P. (2007). Clinical inquiries. What is the best way to evaluate secondary infertility? PubMed, 56(7), 573–575. https://pubmed.ncbi.nlm.nih.gov/17605951

Dhont, N., Lüchters, S., Muvunyi, C. M., Vyankandondera, J., Naeyer, L. D., Temmerman, M., & Wijgert, J. van de. (2011). The risk factor profile of women with secondary infertility: an unmatched case-control study in Kigali, Rwanda. BMC Women s Health, 11(1), 32–32. https://doi.org/10.1186/1472-6874-11-32

Elmohsen, F. R. A., Elsalam, M. A., Ramadan, S. A. E., & Elmoniem, S. O. A. (2023). Study Risk Factors Associated with Secondary Infertility among Infertile Woman Attending Infertility Clinic. Journal of Nursing Science Benha University/Journal of Nursing Science Benha University , 4(2), 716–731. https://doi.org/10.21608/jnsbu.2023.310301

Fan, S., Zhang, Z., Wang, H., Luo, L., & Xu, B. (2024). Associations between tobacco inhalation and semen parameters in men with primary and secondary infertility: a cross-sectional study. Frontiers in Endocrinology, 15, 1396793–1396793. https://doi.org/10.3389/fendo.2024.1396793

Forti, G., & Krausz, C. (1998). Evaluation and Treatment of the Infertile Couple1. The Journal of Clinical Endocrinology & Metabolism, 83(12), 4177–4188. https://doi.org/10.1210/jcem.83.12.5296

Garolla, A., Pizzol, D., Carosso, A. R., Borini, A., Ubaldi, F. M., Calogero, A. E., Ferlin, A., Lanzone, A., Tomei, F., Engl, B., Rienzi, L., Santis, L. D., Coticchio, G., Smith, L., Cannarella, R., Anastasi, A., Menegazzo, M., Stuppia, L., Corsini, C., & Foresta, C. (2021). Practical Clinical and Diagnostic Pathway for the Investigation of the Infertile Couple. Frontiers in Endocrinology, 11, 591837–591837. https://doi.org/10.3389/fendo.2020.591837

Hussain, A., Abbas, M., Zain-ul-Abideen, Mustafa, G., Lateef, M., Mansoor, A., Raza, Y., Hayat, A., & Lashari, M. H. (2025). Innovations and challenges in modern infertility treatment: bridging technology and psychosocial care. Middle East Fertility Society Journal, 30(1). https://doi.org/10.1186/s43043-025-00257-2

Hussain, S. S., & Raees, M. (2024). Causes of Primary Versus Secondary Infertility in Women Undergoing Diagnostic Laparoscopy. BMC Journal of Medical Sciences, 5(1), 22–26. https://doi.org/10.70905/bmcj.05.01.0261

Hussein, H. Y., Kessy, S. A., Luvakule, A. D., -, B. S. K., Khatib, S., Chandika, A. B., Kessy, M. S., & Makubi, A. (2025). Comparative hysteroscopic profiles among women with primary and secondary infertility at Benjamin Mkapa hospital: a cross-sectional study. BMC Women s Health, 25(1), 438–438. https://doi.org/10.1186/s12905-025-03988-6

Jabeen, F., Khadija, S., & Daud, S. (2022). Prevalence of Primary and Secondary Infertility. Saudi Journal of Medicine, 7(1), 22–28. https://doi.org/10.36348/sjm.2022.v07i01.004

Jia, Y., Ai, Z., Zhu, X., Che, Z., Pratikshya, A., Tang, S., & Zhang, Q. (2024). Analysis of predictors of clinical pregnancy and live birth in patients with RIF treated with IVF-ET technology: a cohort study based on a propensity score approach. Frontiers in Medicine, 11, 1348733–1348733. https://doi.org/10.3389/fmed.2024.1348733

Kahan, W., Poborowska, D., Szafrańska, W., Polańska, K., Wojaczek, M., Niedbał, P., Kosińska, A., Kras, M., Lelek, K., & Łata, M. (2024). Impact of pre-conception diet on female infertility. Quality in Sport, 20, 54127–54127. https://doi.org/10.12775/qs.2024.20.54127

Liu, Z., Wang, M., He, S., Wang, X., Liu, X. F., Xie, X., & Bao, H. (2024). Derivation and validation of the first web-based nomogram to predict the spontaneous pregnancy after reproductive surgery using machine learning models. Frontiers in Endocrinology, 15, 1378157–1378157. https://doi.org/10.3389/fendo.2024.1378157

Mansour, H. A. E. (2023). Infertility diagnosis and management. Beni-Suef University Journal of Basic and Applied Sciences, 12(1). https://doi.org/10.1186/s43088-023-00416-2

Marian, S. (2016). Assisted reproductive technology in reproductive medicine — possibilities and limitations. Ginekologia Polska, 87(12), 820–823. https://doi.org/10.5603/gp.2016.0095

Mascarenhas, M., Flaxman, S., Boerma, T., Vanderpoel, S., & Stevens, G. A. (2012). National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Medicine, 9(12). https://doi.org/10.1371/journal.pmed.1001356

Matzuk, M. M., & Lamb, D. J. (2008). The biology of infertility: research advances and clinical challenges. Nature Medicine, 14(11), 1197–1213. https://doi.org/10.1038/nm.f.1895

Merza, L.-E., & Dinu, E. (2025). Impactul factorilor etiologici și de risc asupra infertilității la femei | [The impact of etiological and risk factors on female infertility]. Jurnal Medical Brasovean, 4–17. https://doi.org/10.31926/jmb.2024.2.02

Mongane, J., Hendwa, E., Sengeyi, D., Kajibwami, E., Kampara, F., Chentwali, S., Kalegamire, C., Barhishindi, I., Kujirakwinja, Y., Maningo, J. B., Kasago, B., & Mulinganya, G. (2024). Association between bacterial vaginosis, Chlamydia trachomatis infection and tubal factor infertility in Bukavu, Democratic Republic of Congo. BMC Infectious Diseases, 24(1), 480–480. https://doi.org/10.1186/s12879-024-09379-w

Moridi, A., Roozbeh, N., Yaghoobi, H., Soltani, S., Dashti, S., Shahrahmani, N., & Banaei, M. (2019). Etiology and Risk Factors Associated With Infertility. International Journal of Women s Health and Reproduction Sciences, 7(3), 346–353. https://doi.org/10.15296/ijwhr.2019.57