Although regular ovulation is essential for conception, it is only one part of the reproductive process. Successful fertilisation and implantation also depend on open fallopian tubes, freely moving sperm with healthy DNA, appropriate timing within the menstrual cycle, and a receptive endometrium.
This review covers the seven most clinically significant barriers and the diagnostic tests used to identify them.
Seven reasons ovulation doesn’t guarantee pregnancy
| Reasons | How common | Signs to watch | Test to confirm |
| Egg quality | ~ 35% of cases | Age >35, short cycles, prior poor IVF response, recurrent loss | AMH, antral follicle count (AFC), Day 3 FSH/E2 |
| Sperm factors | 40-50% of cases | No visible cause in the female partner; prior failed cycles | Semen analysis (WHO 2021 criteria); sperm DNA fragmentation |
| Tubal occlusion | 11-35% of cases | History of PID, chlamydia, endometriosis, pelvic surgery | HSG or Hycosy/saline sonogram |
| Uterine factors | ~ 15% of cases | Heavy or irregular bleeding, recurrent implantation failure | Saline infusion sonogram (SIS), hysteroscopy |
| Timing error | Very common | Intercourse only after Ovulation predictor kits (OPK) are positive; cycle tracking by calendar alone | Urine LH+ progesterone on day 21 to confirm ovulation |
| Cervical factors | Less common | History of Large Loop Excision of the Transformation Zone (LLETZ), cone biopsy, cervical stenosis, scant mid-cycle mucus | Post-coital test; cervical mucus assessment |
| Unexplained infertility | 10-15% of couples | Normal investigations across all standard | Full panel completed; laparoscopy may be considered |
Test to request and when to do:
| Test | What it assesses | When to request |
| Semen analysis | Sperm count, motility, morphology (WHO 2021 reference values) | At the same time as the female workup, not after. There should be the first investigation in any couple |
| HSG/saline sonogram (HyCoSy) | Tubal patency, uterine cavity shape | After 6–12 months of trying, or immediately if PID/endometriosis history |
| AMH + Day 3 FSH/E2/LH | Ovarian reserve; pituitary-ovarian axis function | Age ≥35, irregular cycle, suspected PCOS, prior chemotherapy, or before egg freezing. |
| Post-coit | Sperm-mucus interaction; cervical factor | When semen analysis is normal, but conception is failing, there is a history of cervical procedures. |
Male factors – the overlooked Half
50% of all infertility cases involve a male factor, either alone or combined with a female factor.
Despite this, the male partner is frequently evaluated last – or not at all. Semen analysis is inexpensive and non-invasive and should be ordered simultaneously with female investigations, rather than sequentially. Approximately 8-10% of all men show at least one abnormal parameter.
Parameters evaluated include:
- Sperm concentration = ≥16 million/ml
- Total motility = ≥ 42%
- Progressive motility = ≥ 30%
- Normal morphology = ≥ 4%
Reference values: WHO Laboratory Manual for the Examination and Processing of Human Semen, 6th edition (2021)
When to see a fertility specialist
- Under 35: – After 12 months of regular, unprotected intercourse with no conception. An investigation can begin before a referral is made.
- Age 35-40: – after 6 months of trying. Ovarian reserve declines meaningfully in this window; earlier investigation is clinically appropriate.
- Go sooner: – Do not wait if: known endometriosis or PCOS, two or more miscarriages, irregular or absent periods, history of pelvic infection or STI, prior cancer treatment, partner with known sperm abnormality, either partner over 40
Male fertility
Understanding the male hormonal (HPO) Axis
The reproductive system of males is controlled by the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus secretes GnRH (gonadotropic-releasing hormone) in pulses to stimulate the anterior pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH helps to promote sperm production in the seminiferous tubules, and LH stimulates Leydig cells to produce testosterone. Disruption of the HPG axis at any level results in different hormonal signatures that aid in determining the correct diagnosis.
As per the AUA/ASRM 2024 guideline, hormonal evaluation, including FSH and testosterone, should be obtained for all infertile males with oligozoospermia, azoospermia, impaired libido, or atrophic testes, not reserved for complex cases.
| FSH | 1.5-12.4 IU/L | Elevated FSH with azoospermia = primary spermatogenic failure; often untreatable by medical means alone |
| LH | 1.7-8.6 IU/L | Low LH + low testosterone = secondary hypogonadism; pituitary or hypothalamic cause likely |
| Total testosterone | 9.9-27.8 nmol/L | Low testosterone with high FSH/LH = primary hypogonadism; consider karyotype |
| Prolactin | 86-324 mIU/L | Hyperprolactinemia suppresses GnRH and can cause secondary hypogonadism; check if LH/FSH is low. |
| Estradiol (E2) | <180 pmol/L | T:E2 ratio <10 suggests aromatase excess; may respond to aromatase inhibitor therapy |
| Inhibin B | >80 pg/mL | Sertoli cell marker; low inhibin B with normal FSH can indicate early tubular dysfunction |
The three key patterns that guide decision-making in the clinic based on hormone levels:
- Low testosterone and high FSH/LH = Primary hypergonadotropic hypogonadism → test karyotype and Y microdeletion
- Low testosterone and normal or low FSH/LH = Secondary hypogonadism → MRI pituitary and serum prolactin
- Normal testosterone and LH, and elevated FSH = Isolated spermatogenic failure → testis biopsy for azoospermia.
Fertility hormone testing, female panel
An accurately timed hormonal assessment reveals ovarian function, hormonal or endocrine function of the pituitary gland, and the potential for ovulatory issues. The timing of the sample relative to the menstrual period is essential, as most parameters will not be relevant/testable without a cycle-day association.
| Day 2-3 panel | FSH | Ovarian reserve surrogate.
>10IU/L suggests diminished reserve >20IU/L is associated with poor IVF response |
| E2 | Should be <200 pmol/L. Elevated E2 can suppress FSH, masking a poor reserve result | |
| LH | LH: FSH ratio>2 in the context of irregular cycle suggests PCOS | |
| AMH | Cycle-independent. Best single marker of ovarian reserve.
<1.0 ng/mL = low >3.5ng/mL = possible PCOS pattern |
|
| Day 21 Panel | Progesterone | Mid-luteal progesterone ≥30 nmol/L confirms ovulation occurred. The only reliable biochemical proof of ovulation |
| Timing | In irregular cycles: test 7 days before the expected next period, not on day 21 | |
| Additional tests | TSH | Thyroid dysfunction is a reversible cause of ovulatory failure; screen all women with cycle irregularity. |
| Prolactin | Hyperprolactinemia suppresses ovulation; sample before breakfast and physical activity. |
The only hormone that can be reliably measured throughout the menstrual cycle, and therefore is considered to be the best first-line ovarian reserve marker, is Anti-Müllerian Hormone (AMH), especially for women with very irregular cycles for whom a Day 3 sample would be impossible to obtain.
IUI versus IVF – choosing the right pathway
In a retrospective cohort study, the rates of clinical pregnancy were 46% for IVF versus 33.3% for IUI, and live birth rates were 40.7% for IVF versus 27.3% for IUI. The rate of multiple pregnancies was also higher with IVF (15.9%) compared to IUI (6%). These values support a decision framework that considers diagnosis, age, and the number of prior failed treatment cycles, rather than relying on cost alone to guide the patient’s choice of treatment.
| Clinical factor | IUI (intrauterine insemination) | IVF (in vitro fertilisation) |
| Where fertilisation occurs | Inside the fallopian tube (natural) | In a controlled lab environment |
| Success rate (age<35) | 10-20% per cycle | 40-50% per cycle |
| Cost per cycle (USD) | $300-$2,000 (± medication) | $12000-$22,000 (± $3k-$6k medication) |
| Invasiveness | Catheter insemination; no anesthesia | Surgical egg retrieval under sedation |
| Best for | Mild male factor, unexplained infertility, cervical factors, donor sperm use, women <38 with good reserve | Blocked tubes, severe male factor, endometriosis stage III-IV, poor ovarian reserve. Recurrent IUI failure (3+ cycles). Age >38 |
| Embryo selection | Not possible – natural selection only | PGT-A/M available: screen for chromosomal abnormalities before transfer |
| Monitoring burden | 2-3 clinic visits per cycle | 8-12 clinic visits per cycle |
| Multiple pregnancy risk | ~6% (with ovarian stimulation) | ~ 15.9%, reduced by the single embryo transfer policy |
| Clinical guidance | ASRM recommends 3-4 stimulation IUI cycles before escalating to IVF in eligible patients | Immediate IVF is appropriate if indicated; delays reduce cumulative success rates in older patients. |
Tracking ovulation with irregular periods
Why traditional methods don’t work and what alternatives might be better.
The standard approach to calendar-based predictions has a 28-day schedule. An irregular cycle, one in which the cycle length varies by more than 7-9 days, will render this method ineffective for timing purposes. The timing of the LH surge (the peak of your menstrual cycle) has been altered due to PCOS, hyperprolactinemia, thyroid dysfunction, and hypothalamic suppression; therefore, a layered multi-method approach is necessary.
- Quantitative LH monitoring evaluates hormone concentration and identifies surge patterns by testing twice daily starting on cycle days 8–10 or 12–14.
- Basal body temperature (BBT) charting shows ovulation through a sustained temperature rise of 0.2–0.5°C over consecutive mornings, confirming ovulation retrospectively.
- Cervical mucus assessment tracks changes in “egg-white” consistency as estrogen rises, aiding sperm transport.
- Mid-luteal progesterone testing 7 days post-ovulation confirms ovulation with ≥30 nmol/L.
- Follicle-tracking ultrasound visually monitors follicle growth and confirms ovulation, which is especially beneficial for patients with unreliable home methods.
Frequently Asked Questions
References:
- Afkari, M., Saboori-Darabi, S., Shahzadeh Fazeli, S. A., & Amiri-Yekta, A. (2025). Male infertility and its ties to next generation sequencing as a new forward path to definite diagnoses. Gene, 965, 149651. https://doi.org/10.1016/j.gene.2025.149651
- Dhikhirullahi, O., & Zhang, Z. (2025). Male infertility. Systems Biology in Reproductive Medicine, 71(1), 416–438.
- Furini, C., Costantino, F., Granata, A. R., Spaggiari, G., Santi, D., & Simoni, M. (2025). Still counting sperm? Why novel, truly informative measurements of testis function in male infertility are urgently needed. Endocrine, 90(3), 1067–1078.
- Grande, G., Garolla, A., Graziani, A., Astorri, A. L., Cammarota, M. V., Merola, A., Polidori, M. P., Lulli, E., Busato, E., Pesce, F., Pompa, G., Pontecorvi, A., Milardi, D., & Ferlin, A. (2025). Comprehensive diagnostic and therapeutic approach to male factor infertility aimed at natural fertility: A multicentric retrospective cohort study. Andrology, 13(8), 2122–2130.
- Health (UK), N. C. C. for W. and C. (2013). Investigation of fertility problems and management strategies. In Fertility: Assessment and Treatment for People with Fertility Problems. Royal College of Obstetricians & Gynaecologists.
- Kozinszky, Z., Bereczki, K., Vedelek, V., Bicskei, P., Tabi, M., Ekes, C., Lajkó, N., Nagy, O., Sinka, R., Vágvölgyi, A., & Zádori, J. (2024). Pre- and Procedural Factors Influencing the Success of In Vitro Fertilization: Evaluating Embryo Quality and Clinical Pregnancy in Cases of Tubal Factor Infertility. Journal of Clinical Medicine, 13(19), 5754.
- Kumar, N., & Singh, A. K. (2015). Trends of male factor infertility, an important cause of infertility: A review of literature. Journal of Human Reproductive Sciences, 8(4), 191–196.
Anna Haotanto is the Founder of Zora Health and a passionate advocate for women’s empowerment. Anna’s personal experiences with egg-freezing, PCOS, perimenopause and the challenges of fertility have fueled her mission to provide high-quality information, financing, and support to help women and couples navigate their fertility journeys with confidence. She is also recognised for her achievements in finance, entrepreneurship, and women’s empowerment, and has been featured in various media outlets. You can also follow her on Linkedin or Instagram.
