Infertility is defined as the inability of a couple who wants to have a child to achieve pregnancy despite regular, unprotected sexual intercourse. When the woman is <35 years old, it is defined as the absence of pregnancy after 1 year or longer of regular, unprotected sexual intercourse; when she is >  35 years old, it is defined as the absence of pregnancy after 6 months or longer of regular, unprotected sexual intercourse. Some clinicians prefer to use the term ‘‘subfertility’’ to describe failure to conceive unless the couple has been proven to be sterile.

Normal fertility

Fecundability is the probability of achieving pregnancy at the end of one menstrual cycle after unprotected intercourse, and this rate is 20-25% under the age of 35. Pregnancy occurs within the first year in approximately 85% of young and healthy couples. At the end of the 2nd year, the cumulative pregnancy rate is approximately 92%. Fertility, which peaks between the ages of 20-24, decreases as the woman’s age increases. This rate, which is 15-20% between the ages of 30-34, is 25-45% between the ages of 35-39. Similarly, abortion rates also increase in direct proportion to age.

Prevalence

We can say that infertility is a common condition with significant psychological, economic, demographic, and medical effects. Although its incidence has not changed over the years (%13-15), rates of consultation and treatment have increased significantly. Postponement of the desire for pregnancy, developments in assisted reproductive technologies, and increased awareness through the active use of social media platforms have contributed to this.

Causes of infertility

In developed countries, male factor-related causes account for 30-40%, tubal and peritoneal factors for 30-40%, ovulatory factor for 10-20%, uterine factor and other rare causes for 5%, and unexplained infertility for 10-20%. In approximately 30% of cases, more than one cause of infertility is present, and in 40% of couples, there may be a cause related to both the male and the female partner.

Evaluation of infertility: When?

Female age is the most important parameter in the prognostic profile of couples. As a general consensus, evaluation of the couple should begin when pregnancy has not been achieved after 12 months of regular and unprotected intercourse if the woman is < 35 years old, and after 6 months of regular and unprotected intercourse if she is between 35-40 years old. If the woman is older than 40, evaluation should begin within a period shorter than 6 months. Likewise, if there is a history of oligo-amenorrhea, known or suspected uterine/tubal/peritoneal disease, stage 3-4 endometriosis, or known or suspected male subfertility, evaluation should be performed earlier.  During this period, if present in the couple’s history, lifestyle changes such as quitting smoking, limiting caffeine and alcohol consumption, and reaching an ideal body mass index should be recommended.

Evaluation of infertility

The diagnosis, evaluation, and treatment of infertility is a stressful situation for most couples. The clinician should not ignore the couple’s emotional state, which may include depression, anger, anxiety, and marital discord. It should be remembered that many factors couples may have can contribute to their infertility; therefore, a comprehensive initial evaluation including a detailed history and physical examination should be performed. This approach will identify most causes of infertility, if present. Both partners should be evaluated simultaneously. The same approach should be used for both primary and secondary infertility.

Points that should be questioned for the woman during history-taking and physical examination:

  • Duration of infertility and results of previous evaluations and treatments
  • Characteristics of the menstrual cycle (age at menarche, cycle length and characteristics, presence of molimina, and presence/severity of dysmenorrhea)
  • Pregnancy history
  • Previous contraception methods
  • Frequency of coitus and sexual dysfunction
  • Previous surgeries (procedures, indications, and outcomes), pelvic inflammatory disease, sexually transmitted infections
  • Thyroid disease, galactorrhea, hirsutism, pelvic or abdominal pain, and dyspareunia
  • Previous abnormal Pap smear and treatments
  • Current medications and allergies
  • Family history of birth defects, developmental delay, early menopause, and reproductive problems
  • Exposure to known environmental toxins
  • Smoking, alcohol, and addictive drug use

Points to consider during physical examination:

  • Weight, body mass index, and blood pressure
  • Enlargement, nodules, and tenderness of the thyroid gland
  • Evaluation of breast characteristics and secretions
  • Signs of androgen excess
  • Vaginal or cervical abnormalities, secretions, or discharge
  • Pelvic or abdominal tenderness, organ enlargement, or masses
  • Size, shape, position, and mobility of the uterus
  • Adnexal masses or tenderness
  • Cul-de-sac masses, tenderness, or nodularity

Points that should be questioned for the man during history-taking and physical examination:

  • Duration of infertility and results of previous evaluations and treatments
  • Previous surgeries (especially involving the testes and inguinal hernia), history of mumps virus infection
  • Medications used
  • History of chemotherapy and radiotherapy
  • Smoking, alcohol, and addictive drug use
  • Sexual dysfunction and impotence
  • Family history of birth defects, developmental delay, early menopause, and reproductive problems

Points to consider during physical examination:

  • Weight, body mass index, and blood pressure
  • Evidence of hypoandrogenism and gynecomastia
  • Groin, genitalia
    • Presence of inguinal hernia
    • Palpation of the testes for normal position/volume/tenderness
    • Palpation of the epididymides for nodularity/tenderness
    • Evaluation for varicocele
    • Examination of the penis for abnormalities

Diagnostic tests

After history-taking and physical examination, diagnostic testing should begin with the least invasive methods to identify the most common causes of infertility.

First-line diagnostic tests;

  • Semen analysis to evaluate male factor infertility
  • Documentation of normal ovulatory function: women who have regular menstruation approximately every 4 weeks with molimina symptoms are almost always ovulatory. However, when there is any doubt about ovulation or when it needs to be proven, one of the following methods may be used: serum progesterone measurement, urinary luteinizing hormone (LH) kits, serial basal body temperature monitoring, or serial transvaginal ultrasonography monitoring.
  • Evaluation of tubal patency and uterine cavity with hysterosalpingography  (HSG)
  • Evaluation of ovarian reserve with follicle-stimulating hormone (FSH) and estradiol levels on days 2-3 of the menstrual cycle, antral follicle count, and/or anti-Müllerian hormone (AMH)
  •  Thyroid-stimulating hormone (TSH)

Additional tests may be required in selected couples;

  • Evaluation of uterine fibroids and ovarian cysts by ultrasound and other imaging methods when necessary
  • Laparoscopy for the diagnosis of endometriosis and evaluation of other pelvic pathologies
  • Evaluation of the uterine cavity with hysteroscopy and treatment of uterine anomalies such as polyps, submucous fibroids, and septum

In conclusion:

  • Diagnostic evaluation for infertility should include a comprehensive history and physical examination
  • Evaluation of the infertile woman should be accompanied by evaluation of the male factor
  • Evaluation should be performed after 1 year if the woman’s age is < 35, and after 6 months if the woman’s age is > 35
  • Evaluation should be performed without delay in the presence of severe oligomenorrhea/amenorrhea/advanced-stage endometriosis/any condition that may limit fertility
  • First-line diagnostic evaluation for infertility should include evaluation of ovulatory function, evaluation of the structure and patency of the female reproductive system, and semen analysis
  • Ovarian reserve tests should not be performed routinely,

However, they may be used in selected patient groups who will undergo ovarian stimulation with exogenous gonadotropins and who have risk factors for low ovarian reserve.

  • Routine laparoscopy should not be performed in the evaluation of female infertility,

However, it should be performed when there is strong suspicion of advanced-stage endometriosis, tubal occlusive disease, or peritoneal factor.