Infertility: How GPs can help

Defining infertility

Infertility is defined as the absence of a desired pregnancy, following regular, unprotected sexual intercourse, for a period of at least one year. Research suggests that 80 per cent of couples become pregnant during the first year of trying for a baby, while in the second year, another 5 per cent will achieve pregnancy.

Therefore, a couple that fails to conceive after one year of regular sexual intercourse should be considered infertile. It is important that these people start investigations and treatment, as time is a critical factor for those trying for a baby.

If the female is older than 37 years and is not pregnant within six months, they are advised to start fertility investigations immediately. Infertility is significantly associated with the social phenomenon of delaying birth. Almost a third of women who postpone pregnancy to their mid-30s and half of women who postpone pregnancy to the age of 40 will experience infertility.

The availability of information on treatment and new possibilities in diagnosis, as well as a more positive social attitude towards infertility, mean that couples are inclined to seek the help of experts relatively quickly and many will start with their GP.

Normal conception

When you are investigating the reasons for infertility, you will find that it is the result of anatomical, physiological and endocrine irregularities.

To achieve conception, the male partner must be able to enter the appropriate number of functionally-normal sperm in the upper part of the vagina of the female partner.

The man must have adequate spermatogenesis, which includes the successful maturation of sperm in the epididymis, normal sperm transmission, the corresponding function of accessory glands and proper erectile and ejaculatory function.

The female partner must have an ovulatory cycle, adequate cervical mucus that allows the sperm to survive, matching the endometrium in the uterus and patent Fallopian tubes. Disorders of the functions described above lead to infertility.

Why infertility occurs

The causes of infertility can be related to one or both partners. Male factor or insufficient production of sperm is the cause of infertility in 30 per cent of couples. Female factors of infertility are the cause in 50 per cent of couples. The causes of infertility in both partners are found in 20 per cent of couples. In 20 per cent of infertile couples, it is not possible to find a clear reason for infertility. The most common cause of infertility in men is abnormal sperm, while in women the most common problems are ovulatory dysfunction and nonpatent Fallopian tubes (tubal factor).

Infertility diagnosis — What to look for

Male

Causes of male infertility include lack of testicular tissue; disorder of hypothalamus-pituitary; lack or obstruction of vas deferens; erectile dysfunction; primary testicular ejaculatory dysfunction; antispermal antibodies; infection; varicocele; elevated testicular temperature and idiopathic oligozoospermia.

Female

Causes of female infertility include ovulatory dysfunction (genetic diseases of the adrenal glands; autoimmune hyperandrogenaemia; thyroid disease; chemo/ radiotherapy; pituitary disease; excessive exercise; changes in weight; drugs; narcotics); tubal/peritoneal (pelvic inflammatory disease (PID); previous ectopic pregnancy; endometriosis; peritubal adhesions); cervical factor (inadequate mucus, cervicitis); and uterine (fibroids, congenital malformations, intrauterine adhesions). The aim of fertility treatment is successful pregnancy. The main principle of treatment is to achieve the most natural, least complicated and least invasive way to facilitate a woman to become pregnant.

Medical history

When taking the medical history, it is important to find out about possible diseases in the family, including hereditary diseases, tuberculosis and diabetes. Similarly, when prescribing oral hormonal contraceptives, it is important to ask for possible thromboembolic events in patients, which can raise the need for early thrombophilia testing. It is important to accurately take the gynaecological history, including year of first period, date of the last menstrual period, the regularity of the menstrual cycle, its duration, the degree of bleeding, the menstrual pain and premenstrual symptoms. Painful and regular periods implicate the ovulatory cycle. Irregular periods raise suspicion of ovulatory dysfunction. Menstrual periods that are recently painful could indicate possible endometriosis. It is also necessary to have an insight into the number of births, the mode of delivery, complications of childbirth or the postpartum period. It is also important to get insight into historical pregnancies, miscarriages, and abortions if they have taken place and whether there were complications. Previous miscarriages raise suspicion of uterine factor infertility. Postpartum or postabortal fever can be associated with damaged Fallopian tubes. It is necessary to examine whether the woman uses contraception and what type.

Sexual history

The sexual history is also very important as sexually-transmitted infections can negatively affect Fallopian tubes. A history of transient attacks of inflammatory disease of the female reproductive system and/or ectopic pregnancy leads to tubal factor infertility. As part of the diagnostic investigation, the couple is questioned about their sexual life and the frequency of sexual intercourse. If a couple has intercourse every two to three days between menstrual cycles, we can conclude that the couple have a regular sexual life. In patients with ‘normal’ history, we must especially pay attention to the male factor or possible immunological aetiology. It is important to find out whether the male partner has achieved previous pregnancies with other partners and also to take the family and personal medical history including hereditary diseases, endocrine disorders, infectious diseases and mumps.

Physical examination

Physical examination of the patient is directed to the visible anatomical or endocrine disorders. Doctors should pay attention to height, weight, arrangement of body hair, acne on the face of the presence or galactorrhoea.

BMI

Women with a BMI >30 are likely to take longer to conceive, and losing weight could increase the chance for conception. Glucose tolerance test and fasting insulin can be tested in patients with a BMI >30 in order to evaluate whether metformin therapy could help in achieving regular (ovulatory) cycles. Folic acid supplementation is recommended before pregnancy (0.4mg/day).

Smear test

Gynaecological examination and smear test analysis is necessary. While taking the smear test, a doctor should evaluate the appearance and quantity of cervical mucus whose characteristics must match the day of the menstrual cycle. Palpable mass in the pelvis indicates changes of the uterus or ovaries, and they need to be referred to further investigation by ultrasound.

Semen analysis

The male partner should be given a semen analysis, which will give an idea of the fertilising potential of sperm. If semen analysis finds leukocytes, it is advised that a bacteriological examination of the semen and urine (frequent chronic prostatitis) be carried out. Urologists can evaluate infertile men. There is an association between smoking and reduced semen quality, so patients should be advised to stop smoking.

Endocrine tests

The patient is required to do basic laboratory tests, including complete blood count, blood sugar, coagulogram, liver blood tests and urine. It is necessary to check the sex hormones and thyroid hormones. The first blood sample is taken in the very early follicular phase of the cycle, between days two and five, generally preferred day three, when the patient is still bleeding.

Blood is analysed for FSH (hormone that stimulates the follicles), LH (luteinising hormone), estradiol (e2), prolactin (PRL), AMH (anti-Müllerian hormone) and TSH (thyroid-stimulating hormone) and free T4 (thyroxine). AMH is today’s best marker for ovarian reserve.

Low AMH means a low number of eggs and it is often connected with infertility. These patients should be referred to a fertility specialist.

Elevated FSH often correlates with AMH and poor functional ovarian reserve. Unsettled relationship between FSH and LH indicates the possible absence of ovulation (normal ratio FSH>LH).

Increased value of prolactin (PRL) can indicate the presence of a pituitary gland tumour, and abnormal TSH value is associated with thyroid disease. Fertility specialists around the world argue about the normal value of TSH but there is a general consensus that before going into pregnancy (or any stimulation protocol), the level of TSH should be <2.5.

Second blood sampling occurs in the middle of the luteal phase (21-day cycle) and the level of progesterone is measured. If a patient has a regular but long cycle, then the best day for progesterone sampling is not day 21 but it has to be calculated seven days before expected bleeding.

Good values of mid-luteal progesterone are evidence of ovulation. If progesterone is low, we have to suspect that the patient has impaired ovulation or that there is a disorder of the second phase of the cycle.

Ultrasound

Before starting any intervention such as x-ray hysterosalpingography, clomiphene induction of ovulation or laparoscopy, for example, a patient should be scanned with transvaginal ultrasound. Transvaginal ultrasound has a leading role in the diagnostic algorithm and helps identify possible uterine and adnexal pathology and sometimes the cause of infertility including: uterine fibroids, uterine malformations, endometriosis, or hydrosalpinx. Hysterosalpingo contrast-sonography (HyCoSy) is an ultrasound procedure that can detect whether the Fallopian tubes are damaged or blocked. It is sometimes called a tubal patency test or a dye test and can be a substitute for a hysterosalpingography (HSG) or laparoscopy and dye test, without the use of x-rays. Transvaginal ultrasound is necessary to prepare the patient for the procedure of assisted reproduction.