A. Normal Reproductive Cycle
The reproductive cycle of a woman generally runs through three phases, which are controlled by hormonal feedback mechanisms in the hypothalamus and the pituitary gland at the base of the brain. It is usually cyclical, but becomes irregular or ceases altogether if the hormonal balance is disturbed for any reason.
The Follicular Phase
As the levels of progesterone and oestrogen drop at the end of the luteal phase of the previous cycle, the hypothalamus signals to the pituitary gland to increase its production of follicle stimulating hormone (FSH). Under the influence of this hormone 20-30 follicles become active within the ovaries. With increasing age, fewer follicles are present in the ovaries and correspondingly fewer follicles develop during the cycle. The developing follicles produce oestrogen, and as the level of this hormone increases, feedback to the pituitary leads to a decrease in FSH production, until there is only enough to encourage further development of one follicle - the dominant follicle. The increasing amount of oestrogen causes a build up in the thickness of the lining of the uterus (the endometrium) in preparation for pregnancy and changes the cervical mucus so that it becomes favourable to the passage of sperm.
Ovulation
The high level of oestrogen signals the pituitary to release a surge of luteinizing hormone (LH). This hormone triggers the process of ovulation, causing the follicle to mature and release the egg. As the egg is released from the follicle in the ovary, the fimbriated end of the fallopian tube moves across the ovary and collects the egg. If fertilisation occurs it is normally in the widest part of the tube, near the ovary, called the ampulla.
For a couple of days before ovulation, the cervical mucus allows sperm to pass through the cervix and uterus to the fallopian tubes, where it has the ability to live for 2-3 days awaiting the egg. The egg itself is only fertilisable for up to 24 hours, and probably on average less than this.
A layer of cells called the zona pellucida, which after one sperm has penetrated forms a barrier to any others, surrounds the egg. Once inside the egg the sperm releases its contents and the process of fertilisation commences. The fertilised egg starts to divide into cells, the number of cells doubling with each division, and becomes known as an embryo.
The Luteal Phase
The follicle from which the egg was released, now known as the corpus luteum, begins to make progesterone. This hormone acts on the endometrium, along with oestrogen, causing it to enter a secretory phase that enables the endometrium to provide nutrition and a site for implantation to the embryo during pregnancy.
The embryo moves along the fallopian tube and upon reaching the uterus hatches out of its shell some four days later and then invades the endometrium and implants there. The embryonic cells that will form the placenta produce human chorionic gonadotrophin (HCG). The presence of this hormone encourages the corpus luteum to continue making oestrogen and progesterone to support the pregnancy, until the placenta can take over. HCG is the hormone measured in pregnancy tests.
If fertilisation fails or does not take place, then in the absence of HCG the corpus luteum fails leading to a fall in oestrogen and progesterone levels. Without these hormones the endometrium breaks down and menstruation starts. The cycle is now about to start again.
Sperm Production
Sperm production commences in the male at puberty, when primitive sperm cells (spermatogonia) begin to change into mature spermatozoa. It takes approximately 72 days for the sperm cell to form and mature before ejaculation. During this time any severe illness that causes a disruption to production can have an effect on the sperm picture for up to 3 months after the initial episode.
Sperm are produced by repeated division of cells in the small coiled tubules within the testis at an average of about 100 million a day in healthy young men. While in the tubules sperm are nourished by the Sertoli cells. Between the tubules are the Leydig cells, which produce testosterone. Leading from each testis is a long highly coiled tube called the epididymis. As sperm pass through this they mature, becoming able to swim and penetrate the egg cell. They are then transported through the tail of the epididymis via the vas deferens to the urethra and out of the penis as ejaculate.
The seminal vesicles, prostate gland and bulbourethral glands secrete most of the volume of semen - these secretions help deliver the sperm during ejaculation. The volume of spermatozoa from the testes and epididymis is less than 5% of the total semen volume. During ejaculation the sperm and prostatic fluid are ejected first, followed by the seminal vesicle fluid.
The structure of the spermatozoon comprises a head containing the genetic material to be used during fertilisation and a tail that is used for propulsion. While passing along the fallopian tube in the woman the sperm undergoes capacitation. This process involves the removal of a coating of protein that covers the head of the sperm, enabling the sperm to penetrate the egg. Sperm require motility to move through cervical mucus and to pass through the outer coverings of the egg, and a normal shaped head to bind to the surface of the egg. In addition, the release of enzymes from the acrosome on the head of the sperm and vigorous motility are needed to penetrate into the egg to deposit genetic material.
The function of the testes is dependent on hormones from the pituitary gland - follicle stimulating hormone (FSH) and luteinizing hormone (LH). The levels of these hormones rise during the early stages of puberty and stimulate testicular development. LH controls production of the male sex hormone, testosterone, which in turn is responsible for the masculine development that occurs at puberty.
B. Fertility Evaluation
Investigations
Many of the investigations involved in determining why a woman is not conceiving can be done by a general Gynaecologist. Indeed, some of the basic investigations can be carried out by your General Practitioner. You may need referral to an Infertility Specialist for the full range of infertility investigations, however, and a discussion of the relevance of test results to your infertility problem. A referral may be made to an Infertility Specialist directly from the General Practitioner, or from a Gynaecologist. An Infertility Specialist is a doctor who has specialised in Reproductive Medicine.
Investigations of the male and female will usually take place at the same time. A referral to an Andrologist, a specialist in male reproductive disorders, may be made if certain male problems are found.
The fertility evaluation consists of a range of common tests. The sequence of tests may vary according to the individual situation, but the general rule is to proceed from the simple and risk-free tests to those which are more invasive, and to evaluate both partners simultaneously. Infertility is a shared concern, wherever the problem may reside. Therefore, limiting the evaluation to one member of a couple is inappropriate.
- 1. History and physical evaluation.
The evaluation begins with information regarding:
o Past medical and surgical events
o Current health status, including diet and lifestyle
o Occupational risks
o History of sexual development and relations, including birth control, pregnancies, current relationship and practices.
Examination of the woman consists of a general physical and a more detailed examination of the pelvic area often using an ultrasound. The internal (pelvic) examination is helpful in providing information about the size, shape and position of the reproductive organs.
The male evaluation consists of a general physical, and more detailed examination of the penis, scrotum and testes.
- 2. Laboratory Studies
At the time of the initial visit some laboratory studies may be done. If a Pap smear is due to be performed, this may be done at this time. Many consultants do a routine Pap test on the woman during her internal examination to rule out cervical cancer. Women with irregular or absent menstrual cycles may have blood tested for pituitary, thyroid and ovarian hormone levels to check for pituitary dysfunction, ovarian failure or polycystic ovary syndrome. Other tests, including hormonal profiles may be ordered on each partner, as indicated by the history or physical examination. All women should be immune to rubella (German Measles), and to varicella (Chicken Pox). This is easily checked by a blood test. If a woman is non-immune (ie susceptible to rubella or varicella infection), vaccination would usually be advised. Folic acid administration is usually advised.
- 3. Semen Analysis
The semen analysis is the most important test in the evaluation of the male. The test gives an accurate measurement of the number of sperm (stated in millions per ml), the motility of the sperm cells, the size and shape of the sperm cells, the volume and consistency of the ejaculate. The examination should be performed on a fresh specimen within two hours of collection in a sterile container. It is obtained by masturbation and the entire ejaculate should be collected.
Standards vary from laboratory to laboratory, and as it is important for IVF purposes to have the percentage of normal morphology (shape) accurately assessed, your consultant may order the test to be repeated, where more extensive testing of semen for sperm antibodies or for penetration defects may also be performed.
Where abnormalities are found on semen analysis, repeat tests are often required to assess the type and degree of the problem found.
Diagnosis of causes of male factor infertility may require blood tests for the hormones FSH, and testosterone, which play a role in the development and maturation of sperm. A karyotype (chromosome analysis) and other tests may be ordered if the sperm count is very low or zero.
- 4. Diagnostic laparoscopy and hysteroscopy
This test is an important part of the evaluation of many couples. It is generally reserved for the end of the evaluation process.
Laparoscopy is done under general anaesthesia with small incisions made at the umbilicus and the pubic hairline. A laparoscope (a fibreoptic telescope) is passed through the umbilical incision and the ovaries, fallopian tubes, uterus and pelvic cavity can be viewed for abnormalities. Tubal patency can be checked by injecting dye through the uterus and observing it spill through the fimbriated ends of the fallopian tubes. Hysteroscopy may also be performed, using another fibreoptic device called a hysteroscope. It provides direct visualisation of the uterine cavity for growths, adhesions and abnormal anatomy. Increasingly, laparoscopy is omitted in couples where the need for IVF is obvious from the history or analysis of test results.
- 5. Sonohystogram
This is a non-invasive test, which gives some valuable information about the anatomy of the uterine cavity and the patency of the tubes. This involves an ultrasound with the concurrent speculum examination, and insertion of a tiny tube into the cervix to pass dye through the uterine cavity and tubes. A similar technique using Xray technology may also be used. It is called a hysterosalpingogram. These techniques are often performed instead of a laparoscopy and hysteroscopy.