Infertility (female)

Female infertility is defined as the inability of a couple to conceive with regular intercourse without use of contraception after 12 months in women less then 35 years of age, and after 6 months in women 35 years and older.

We can distinguish primary and secondary infertility. In primary, the woman has never achieved pregnancy, while in secondary, there’s been at least one previous pregnancy.

Fecundability is also relevant. It’s the probability of achieving a pregnancy in one menstrual cycle. This number is maximally around 25%, but it decreases with the age of the woman. In a 40 year old woman, the number is only a few percent.

In Hungarian literature, the terms infertility and sterility are usually distinguished. Sterility is defined as how infertility is defined above, but infertility is defined as the inability to carry out a pregnancy.

Infertility is relatively prevalent. In women 15 – 34 years old, it affects 7 – 9%. In women from 35 – 45, the number is 25 – 30%.

Etiology

The cause of infertility according to gender is distributed like this:

• 40% of cases are due to male infertility
• 45% of cases are due to female infertility
• 10% of cases are due to both
• 5% of cases are unknown

The causes of female infertility are as follows:

• Functional infertility
  • Disorders of the hypothalamic-pituitary-ovarian axis causing anovulation
    • Same disorders as of amenorrhoea
  • Disorders of the adrenal gland
  • Disorders of the thyroid gland
  • Anorexia nevrosa
  • Obesity
  • Stress
• Organic infertility
  • Endometriosis (adhesions, abnormal „interleukine millieau”)
  • Fallopian tube disorders (occlusion, infection, ciliary motility problems)
  • Uterine abnormalities (Mullerian disorders, Asherman syndrome, fibroids)
  • Cervical abnormalities (conglutination, mucous and immunological problems)
  • Vaginal abnormalities (septum)

However, the most common causes are increased age, hypothyroidism, endometriosis, PCOS, etc.

The causes of male infertility are as follows:

• Endocrine disorders
  • Hypothalamic dysfunction (Kallman syndrome)
  • Pituitary dysfunction (hyperprolactinaemia)
  • Thyroid disease
  • Steroid use
• Spermatogenesis abnormalities
  • Mumps
  • Varicocoele
  • Heat, radio, chemo
  • Orchitis
• Sperm motility abnormalities
  • Posttesticular obstruction
  • Epididymitis
• Sexual dysfunction
  • Retrograde ejaculation
  • Impotence

Kallmann syndrome is characterised by the absence of GnRH-producing cells in the hypothalamus as well as anosmia.

Diagnosis and evaluation

Thorough history is important. It’s important to evaluate:

• Duration of infertility
• Menstrual history
• Diseases which can cause infertility
• Previous surgeries, especially gynaecological
• Sexual history
• Family history
• Stress, smoking

Physical examination may reveal features of the underlying cause, such as:

• BMI, abdominal obesity
• Incomplete secondary sexual characteristics
  • (hypogonadotropic hypogonadism, Turner syndrome)
• Galactorrhoea, hirsutism, acne, male pattern baldness
  • (hyper- or hypothyroidism, hyperprolactinemia, polycystic ovary syndrome, adrenal disorder)
• Tenderness or masses in the adnexae
  • (chronic pelvic inflammatory disease)
• Palpable tender nodules
  • (endometriosis)
• Vaginal/cervical structural abnormalities, discharge
  • (müllerian anomaly, infection)
• Uterine enlargement, irregularity, or lack of mobility
  • (leiomyoma, endometriosis, adhesions)

Semen analysis is important, to look for oligoszoospermia, asthenozoospermia, teratozoospermia, etc. Semen should be collected after 3 – 5 days of ejaculatory abstinence, and collected in special rooms in the clinic or at home but examined within one hour.

The following as well:

• Evaluation of the ovulatory function is also important and is covered in topic B4.
• Laboratory evaluation of thyroid disorders, prolactin disorders, PCOS, etc.
• Assessment of uterine cavity and fallopian tube patency
  • By hysterosalpingography or hysterosalpingo-contrast-sonography
  • Only for uterine cavity: hysteroscopy, saline hysterosonography

Medical history and labs

The regularity of the menstrual cycle is important in assessing the ovarian cycle. A cycle is considered normal when it comes every 24 – 38 days.

Elevated serum progesterone over a certain value (> 3 ng/mL or > 10 nmol/L) mid-luteal phase (day 21) is indicative of ovulation. If this increase does not occur, the patient has anovulation and should be investigated for it.

Over-the-counter urinary ovulation prediction kits which detect LH in the urine can also be used to predict the timing of the LH surge that indicates ovulation.

Ovarian reserve assessment

Decreased ovarian reserve refers to decreased oocyte quality, quantity, or reproductive potential. These techniques can estimate the number of eggs in the ovaries (ovarian reserve) and is useful in the management of infertility. They can guide the choice and amount of medication to be given.

The two most commonly used tests nowadays are anti-Müllerian hormone (AMH) measurement and antral follicle count (AFC).

AMH is produced by granulosa cells in preantral follicles and is constant throughout the cycle. Normal values are between 1,1 – 3,5. If the value is below this, the ovarian reserve is low, if above then the ovarian reserve is high.

Antral follicle count is an ultrasound measurement of the 2 – 10 mm follicles in the ovaries at the beginning of the cycle. This number correlates to the number of eggs. < 7 AFC means low ovarian reserve, > 20 AFC means high ovarian reserve.

Other tests of ovarian reserve include:

• FSH/oestradiol ratio on day 3
• Inhibit B level
• Clomiphene citrate challenge test

The ovarian reserve declines by approximately 5% per year.

Anatomic and endometrial evaluation

Evaluation of the endometrial thickness and phase by ultrasound is used.

Hysterosalpingography or sonohysterography may be used to evaluate the uterine and fallopian tubes for anatomical abnormalities, endometrial polyps, fallopian tube patency, etc.

Hysteroscopy and MRi may also be helpful.

Hormonal evaluation

Further hormonal evaluation of thyroid function, prolactin, and androgens may be useful as disorders of these are associated with adverse reproductive outcomes.

Basal body temperature test

Progesterone increases body temperature and is released after ovulation. By measuring the body temperature daily in the morning before doing anything which can alter the temperature (walk, eat) for multiple cycles, it’s possible to estimate when during the cycle ovulation occurs. However, the temperature increase occurs too late to be useful for timing intercourse.