Chapter 17 Infertility
Infertility
Approximately one in seven couples has difficulties in conceiving. In general, 80% of the couples who have regular sexual intercourse and do not use contraception will get pregnant within a year. The majority of the remaining 20% achieve a pregnancy within 2 years of trying.
Percentage of couples pregnant after varying time periods of unprotected intercourse (Gutmacher 1965)
Primary infertility is a condition where a couple, who have had no previous pregnancies, are unable to conceive.
Secondary infertility is a condition where a couple, who have had at least one previous pregnancy that may have ended in a livebirth, stillbirth, miscarriage, ectopic pregnancy or induced abortion, are unable to conceive.
Aetiology of Infertility Lifestyle factors such as heavy smoking or being significantly over- or underweight and stress can adversely affect both male and female fertility.
Infertility
Causes of female factor infertility
With increasing age, women become less fertile.
There are many causes of infertility (see below). Sometimes, failure to conceive can be due to a combination of factors. However, in approximately 30% of cases, a clear cause is never established.
| Unexplained infertility | 28% |
| Male factor infertility | 21% |
| Ovulatory disorders | 18% |
| Tubal disease | 14% |
| Endometriosis | 6% |
| Coital problems | 5% |
| Cervical factors | 3% |
Other factors that may play a part include chronic medical conditions such as diabetes, epilepsy and thyroid and bowel diseases.
Causes of male factor infertility
Infertility is often thought of as a female issue, but in around 30% of cases, it is because of a problem in the male partner. As in women, male fertility is also thought to decline with age, although to what extent is unclear. Possible causes of male infertility include:
Investigations
Investigations in the primary setting
When a couple presents to their general practitioner with the issue of infertility, these initial investigations should be carried out.
| Female partner | Cervical smear test. |
| Urine test for Chlamydia (this can cause blockages of the fallopian tube). | |
| Serum progesterone level to check ovulation. This is taken 1 week prior to menstruation, hence day 21 for a 28-day cycle or day 28 for a 35-day cycle (see below). | |
| Rubella immunity – if rubella is contracted during the first 3 months of pregnancy it can seriously harm the developing fetus Women who are not immune to rubella should be vaccinated, and advised to avoid pregnancy for 3 months. | |
| Measuring serum FSH (follicle stimulating hormone), LH (luteinising hormone) and oestradiol to identify hormone imbalances or possible early menopause. | |
| Male partner | Semenalysis to check for abnormalities of the sperm such as number, motility, and morphology (see below). |
| Urine test for Chlamydia, which, in addition to being a known cause of infertility in women, can also affect sperm function and male fertility. |
Investigations in the secondary setting
These are done in the context of a tertiary fertility clinic and after the primary investigations have been carried out. Some or all of the following tests will be done:
| Female partner | Measuring serum FSH, LH and oestradiol to identify hormone imbalances or possible early menopause. |
| Serum progesterone level to check ovulation. This is taken 1 week prior to menstruation, hence day 21 for a 28-day cycle or day 28 for a 35-day cycle. | |
| A pelvic ultrasound scan to look at uterine and ovarian anatomy. | |
| Serial ultrasound tracking of the ovaries for looking at developing follicles (see below). | |
| Checking of tubal patency – either by hysterosalpingogram, hysteron-contrast sonography or laparoscopic hydrotubation. | |
| Diagnostic laparoscopy – to check for problems with tubal and uterine anatomy. | |
| Hysteroscopy – to check for uterine conditions such as fibroids or polyps | |
| Endometrial biopsy (in rare cases) see below. | |
| Male partner | Semenalysis to check for abnormalities of the sperm such as number, motility and morphology (see below). |
| Sperm antibody test to check for protein molecules that may prevent sperm from fertilising an egg. |
Evidence of ovulation
Features suggestive of ovulation
Regular menstruation is usually associated with ovulation, however, no clinical symptoms or signs are sufficiently reliable to confirm ovulation. Supportive laboratory tests are always required.
The secretion of progesterone by the corpus luteum induces a rise of around 0.5 °C in basal body temperature (BBT). If BBT is recorded throughout the menstrual cycle, a fall in temperature is often observed at the time of the LH surge. Charts typical of those generated by A) a woman with a normal ovulatory cycle, and B) a woman with an anovulatory cycle, are shown below. The differences in BBT between ovulatory and anovulatory women are not sufficiently consistent for a diagnosis of ovulation to be made without further tests.
Tests that confirm the occurrence of ovulation
Estimation of serum progesterone is a simple method for confirming ovulation. Progesterone is produced by the corpus luteum and its levels reach a peak in the mid-luteal phase (i.e. 7 days prior to menstruation). If the measured serum progesterone levels are low, this may indicate either that the patient is not ovulating, or that the blood sample was withdrawn at an inappropriate time in the cycle. Information about the time of the subsequent menstrual period is required to accurately interpret the relevance of serum progesterone levels.
The presence of a secretory endometrium confirms that ovulation has taken place. Under the influence of progesterone, the endometrial glands dilate, and secretory vacuoles may be observed within the glandular cells. If an endometrial biopsy is taken in the luteal phase and examined histologically, secretory changes can be observed. A biopsy of the endometrium is a relatively invasive process, but it gives useful information, especially if sensitive progesterone assays are unavailable.
Over the course of the menstrual cycle, an ovarian follicle develops, grows to 20 mm and the oöcyte is then released at ovulation. This process can be visualised by a transvaginal ultrasound examination every 2–3 days during the follicular, ovulatory and early luteal phases. This procedure is too invasive and expensive to be used in an unselected population of women complaining of infertility. However, it is often used to monitor the number and size of the developing ovarian follicles in women undergoing ovulation induction. The serial ultrasound is the only method of detecting the luteinised unruptured follicle syndrome (LUF).
Seminal analysis
Tests which confirm normal sperm production
Semen Analysis
A basic semen analysis assesses the number, morphology and motility of spermatozoa. The patient is asked to provide a sample (usually by masturbation), which should be analysed within 2 hours of production. The sample should be kept warm (15–38 °C) during the interval from production to analysis. Abstinence from sexual activity for a period of 2–3 days is required before submitting a sample for analysis; otherwise an abnormally low count may be recorded. The patient should also be advised to keep the sample away from spermicidal agents, such as those in condoms.
The criteria for normal spermatogenesis may vary from laboratory to laboratory. The WHO criteria are shown below:
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