Infertility

Published on 10/03/2015 by admin

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Chapter 17 Infertility

Infertility 358

Causes of Female Factor Infertility 359

Causes of Male Factor Infertility 359

Investigations 360

Investigations in the Primary Setting 360

Investigations in the Secondary Setting 360

Evidence of Ovulation 361

Features Suggestive of Ovulation 361

Tests that Confirm the Occurrence of Ovulation 362

Seminal Analysis 364

Tests which Confirm Normal Sperm Production 364

Sperm Production Tests 365

Abnormalities in Sperm Production 366

Sperm Function Tests 367

Postcoital Test 367

Measurement of Antisperm Antibodies 367

In Vitro Assessment of Fertilisation Ability of Sperm 367

Abnormal Sperm Function 367

Tests of Tubal Patency 368

Requirements for the Assessment of Tubal Patency 369

Contraindications to the Assessment of Tubal Patency 369

Assisted Conception 370

Assisted Reproduction Techniques 370

Fertility Drugs 371

Tubal Surgery 373

Efficacy 373

Side Effects 373

Assisted Conception 380

Counselling 380

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)

Definitions

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.

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).
Male partner	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).
Male partner	Sperm antibody test to check for protein molecules that may prevent sperm from fertilising an egg.

Evidence of ovulation

Features suggestive of ovulation

1. Clinical symptoms and signs

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.

2. Changes in basal body temperature

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.

A. Normal BBT chart from an ovulating woman

B. Abnormal BBT chart from a woman who is not ovulating

Tests that confirm the occurrence of ovulation

1. Serum progesterone levels

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.

2. Endometrial biopsy

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.

3. Serial ovarian ultrasound

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).

Early follicular phase (no ovarian follicle visible on ultrasound).

Mid-follicular phase (12 mm follicle visible on ultrasound).

Immediate pre-ovulatory phase (ovarian follicle on 20 mm diameter).

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:

1. Volume: ≥2 ml

2. Concentration: ≥20 million/ml

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