Causes of Infertility in Women and Men, and the Workup

The causes of infertility in women and men fall into a short list: in women, problems with ovulation, the fallopian tubes, the uterus and endometriosis; in men, problems with hormones, sperm production or sperm transport; and in many couples, no cause that standard tests can find. Smoking, alcohol and body weight act on both partners. Because each cause leads to a different treatment, both partners are evaluated at once.

That is the core of how Dr. Parul Prakash, Head - Reproductive Medicine (IVF), Artemis Hospitals, Gurugram, India, approaches a couple who have not conceived. This article sets out the causes she described, the workup she uses, and the semen analysis standards that decide whether a male factor is present. For the wider picture of fertility and age, and of when IVF or egg donation becomes the right answer, see the complete guide to IVF, ICSI and egg donation.

Lifestyle factors that affect fertility

Dr. Prakash lists smoking, alcohol and body weight among the lifestyle factors that affect fertility, and lifestyle modification is the first treatment she names.

Smoking. Smoking accelerates the loss of reproductive function and brings menopause forward by one to four years. In women it is associated with a higher risk of miscarriage and of ectopic pregnancy, in which the embryo implants outside the uterus, usually in the fallopian tube. In men it damages semen parameters.

Alcohol. Dr. Prakash sets the threshold at more than two drinks a day.

Caffeine. High caffeine intake is commonly cited alongside these factors; moderate intake, of the order of one to two cups of coffee a day, has not been shown to reduce fertility.

Body weight. Dr. Prakash flags a body mass index (BMI) above 30. Being markedly underweight, with a BMI below about 19, also disrupts ovulation. When she turns to treatment, weight reduction is the first lifestyle change she names.

Diet

Her dietary advice favours a high intake of fruit and vegetables, olive oil, and low-fat dairy products, a Mediterranean-style pattern.

Causes of infertility in women

Ovulatory problems and PCOS

Polycystic ovary syndrome (PCOS) is a hormonal disorder in which ovulation is irregular or absent. On ultrasound, Dr. Prakash pointed out the characteristic picture: many small follicles crowded into one ovary. Most women with PCOS are first treated with ovulation induction, using tablets or injections to trigger the release of an egg. Where several cycles of ovulation induction fail, IVF becomes the indicated treatment.

Endometriosis

Endometriosis is a condition in which tissue similar to the lining of the uterus grows outside it, typically on the ovaries, tubes and pelvic lining, causing inflammation, scarring and pain. Dr. Prakash's position is that in severe endometriosis, IVF is the treatment to offer. Severe disease scars and distorts the tubes and ovaries that natural conception depends on.

Tubal disease

The fallopian tube is where egg and sperm meet and where the early embryo begins its journey, so tubal damage is a direct mechanical cause of infertility. Dr. Prakash distinguishes two situations:

• Hydrosalpinx, a blocked tube that has become dilated and filled with fluid. Her practice is to remove it surgically. The fluid can flow back into the uterus and lowers the chance of an embryo implanting, which is why a hydrosalpinx is removed or disconnected from the uterus before IVF.
• Bilateral tubal block, in which both tubes are blocked. Egg and sperm cannot meet, and IVF is the treatment, since it bypasses the tubes entirely.

Problems inside the uterus

Three abnormalities of the uterine cavity can prevent an embryo from implanting, and Dr. Prakash treats each surgically:

• Submucosal fibroids, benign muscle growths that bulge into the cavity, are removed.
• Endometrial polyps, overgrowths of the lining, are removed by polypectomy.
• Intrauterine adhesions, bands of scar tissue inside the cavity, are cut.

All three are usually treated through hysteroscopy, in which a thin camera is passed through the cervix into the uterus, without any abdominal incision.

Unexplained infertility

Unexplained infertility is a common diagnosis. The ovaries, tubes, uterus and semen all appear normal, yet the couple does not conceive. Dr. Prakash's explanation is that the problem lies in an intrinsic defect at the level of the ovaries, the uterus or the sperm that routine tests cannot detect, and which can lead to fertilisation failure. Unexplained infertility is accordingly on her list of indications for IVF. The laboratory can reveal, and partly overcome, a fertilisation problem that is invisible in the clinic.

How sperm are made and delivered

Male infertility is easiest to understand by following the path of a sperm. Dr. Prakash traced it step by step:

1. Sperm begin as small round cells in the testes.
2. They mature under the influence of hormones.
3. They pass to the epididymis, a coiled tube behind each testis, where they acquire the ability to swim.
4. They travel through the vas deferens, the duct that carries sperm towards the urethra.
5. They take up nutrition from secretions of the seminal vesicles and prostate, which make up most of the volume of semen.
6. They leave through the urethra at ejaculation.

A failure at any point in this chain produces a distinct type of male infertility.

Causes of infertility in men

Dr. Prakash groups the causes by where the chain breaks:

• At the level of the brain. The brain does not produce the hormones that drive sperm production. Clinically this is hypogonadotrophic hypogonadism, a failure of the hypothalamus or pituitary gland.
• In sperm production. The testes themselves produce few or no sperm. She named infection and varicocele, a set of enlarged veins in the scrotum, among the causes.
• In sperm transport. A blockage along the ducts prevents sperm from reaching the ejaculate even though production is normal, which results in obstructive azoospermia (no sperm in the semen because of an obstruction).
• In erection or ejaculation. Erectile and ejaculatory problems, including those caused by certain medications, prevent sperm from being delivered.

The distinction between obstructive and non-obstructive causes matters for treatment. Where production is intact and only transport is blocked, sperm can usually be retrieved directly from the epididymis or testis and used for ICSI, as described in the IVF and ICSI process article. Where varicocele is the cause, surgical correction is an option; costs are listed on the varicocelectomy cost page.

The infertility workup for both partners

Dr. Prakash's rule is that both partners are evaluated at the same time. The core investigations are few, and each answers a specific question.

Ultrasound

A pelvic ultrasound assesses three things at once: ovulatory function (whether follicles grow and release an egg), ovarian reserve (how many eggs remain, judged from the count of small follicles in the ovaries), and the uterine cavity (fibroids, polyps and the quality of the lining).

Tubal patency

Whether the tubes are open is tested by hysterosalpingography (HSG), an X-ray in which dye is passed through the cervix and its flow through the uterus and out of the tubes is observed.

Blood tests and semen analysis

For doctors referring couples from abroad, Dr. Prakash asks for blood tests and a semen analysis to be done at the referring end.

Semen analysis normal values and what they mean

A semen analysis reports the volume of the sample, the total sperm count, the concentration, the motility and the morphology. Dr. Prakash gave the reference values she uses:

• Concentration: at least 15 million sperm per millilitre.
• Motility: at least 40% of sperm moving.
• Morphology: at least 4% of sperm normally shaped.

These are the lower reference limits of the World Health Organization's 2010 manual; the 2021 edition revised them slightly, to 16 million per millilitre and 42% motility, with morphology unchanged at 4%.

A normal sperm has a head, a neck and a tail. Good motility means sperm that are highly progressive, swimming forward in a straight line rather than circling or twitching in place. Azoospermia is the complete absence of sperm in the sample.

Collecting the sample correctly

A semen analysis is only as reliable as the sample, and Dr. Prakash treats collection as a clinical step in its own right:

• Abstinence: the sample should be collected after a minimum of two days and a maximum of seven days of abstinence.
• Method: the sample is produced by masturbation.
• Place: in a private room near the laboratory, so that it reaches the laboratory quickly.
• Container: a wide-mouthed plastic jar.
• Completeness: the whole sample must be collected, because the first portion of the ejaculate contains the largest number of sperm. Losing it can make a normal sample look abnormal.
• Handling: the sample is kept in an incubator at body temperature until it is analysed.

Matching each cause of infertility to its treatment

The workup sorts couples into treatment paths. Lifestyle factors are corrected first: weight reduction and stopping alcohol and smoking. Structural problems inside the uterus are corrected surgically; costs for these procedures are on the hysteroscopy cost page and the myomectomy cost page. Bilateral tubal block, severe endometriosis, low ovarian reserve, severe male factor, repeated failure of ovulation induction and unexplained infertility lead to IVF, with ICSI where the male factor demands it.

Dr. Prakash's full list of IVF indications is discussed in the complete guide, and the laboratory steps that follow are set out in the IVF and ICSI process article.