The Investigation of Infertility- Chapter 9:

Q 9. 1 What is infertility?

Infertility is usually defined as involuntary failure to conceive after one year of unprotected sexual intercourse. In its wider sense, infertility refers to couples who are having difficulty achieving parenthood and would, therefore, include pregnancy problems such as recurrent miscarriage (Q12.9). Between 80-90% of couples who will achieve a pregnancy without assistance, succeed within the first year of unprotected intercourse and about 95% within two years. The central theme of biology is reproduction, and for those unfortunate couples who have difficulty achieving parenthood there may be feelings including anxiety, frustration and despair.

Primary infertility usually refers to patients with no history of a successful pregnancy. Secondary infertility indicates that there has been a previous successful pregnancy. It may also be appropriate to consider whether the infertility is primary or secondary for each partner as well as for the current partnership.

References:

Estimates of human fertility and pregnancy loss (1996) 09-01-1213.

Background pregnancy rates in an infertile population (1996) 09-01-1346

Q 9. 1 What is infertility?
Q 9. 2 How common are infertility problems?
Q 9. 3 What are the main causes of infertility?
Q 9. 4 What are the objectives of our infertility investigations?
Q 9. 5 Have there been any noticeable changes in fertility requirements in recent years?
Q 9. 6 What is the effect of our age on fertility?
Q 9. 7 I smoke cigarettes. Can this have an effect on my fertility?
Q 9. 8 Does my weight influence fertility?
Q9. 8A How can I lose weight?
Q 9. 9 I have fibroids. Could these reduce my fertility?
Q 9. 10 I have been told that my womb has an abnormal shape and that was the way that I was born. Could this reduce my fertility?
Q 9. 11 I have endometriosis. Could this reduce my fertility?
Q 9. 12 I have been told that I have cervicitis or a cervical ectopy (erosion). Could this impair my fertility?
Q 9. 13 My doctor tells me that my womb is retroverted (tilts backwards). Could this reduce my fertility?
Q 9. 14 I have had an ectopic pregnancy. Does this affect my future fertility?
Q 9. 15 We are worried that we may have a fertility problem. What should we do?
Q 9. 16 How will our doctor be able to identify the cause of our infertility?
Q 9. 17 How can we tell if I am releasing my eggs (ovulating)?
Q 9. 18 Investigations have shown that I have a problem releasing my eggs (anovulation). What could be the cause of this?
Q 9. 19 How important are my Fallopian tubes in fertility?
Q 9. 20 How can we tell if my Fallopian tubes are functioning?
Q 9. 21 How can we assess male fertility?
Q 9. 22 What is the purpose of a post-coital test (PCT)?
Q 9. 23 We have had our infertility investigations and our problem remains unexplained. How can this be?
Q 9. 24 What are our chances of achieving a pregnancy?
Q 9. 25 Where can I obtain more information?
Q 9. 26 Could I have some useful Web sites?
Women’s Health – Home Page

Q 9. 2 How common are infertility problems?

It has been estimated that one couple in six will have been concerned about their fertility and about 10% of couples are currently experiencing fertility difficulties. In a Danish study of 3,743 randomly selected women aged 15 to 44 years, 27.2% of those planning a family had experienced fertility delays.

References:

Infertility-epidemiology and referral practice (1991) 09-02-2089

Q 9. 3 What are the main causes of infertility?

The essential requirements for a couple to be fertile are healthy sperm which must be deposited at ejaculation at the cervix, ovaries that are releasing eggs (ovulation), fallopian tubes that are open and healthy and womb capable of nurturing a pregnancy (Figure 9.1).

The three most common causes of infertility are:

• anovulation (eggs are not being released).

• tubal factor (Fallopian tube disease).

• male factor infertility (Q9.21).

Infertility remains unexplained in about 25% of couples following investigations to identify obvious problems in these three areas.

References:

Return of fertility in nulliparous women after discontinuation of the intrauterine device: Comparison with women discontinuing other methods of contraception (2001) 09-03-3344

Infertility-epidemiology, aetiology and effective management (1995) 09-03-2089

Infertility-epidemiology and referral practice (1991) 09-03-967a.

[An epidemiological study of 1000 sterile couples]. Spanish 09-03-2860

Population study of causes, treatment, and outcome of infertility (1985) 09-03-1078

Q 9. 4 What are the objectives of our infertility investigations?

The objectives in requesting infertility investigations for you are initially to identify factors that may be contributing to delay in achieving a successful pregnancy and subsequently to monitor your response to treatment.

Q 9. 5 Have there been any noticeable changes in fertility requirements in recent years?

In western society, the survival rate of babies and infants has improved and most couples avoid having large families. Quality of life rather than quantity is the pre-requisite. Effective family planning methods, such as the combined oral contraceptive pill, allow modern couples the facility to delay childbearing until socially convenient. In France, the average age of first pregnancy is 28 years compared to 24 years in 1970 and there has been a doubling in the proportion of women giving birth for the first time after 30 years of age since 1972.

There was a 25% increase in the number of couples requesting infertility services in the USA from 1982 to 1988. The prevalence of infertility remained unaltered over a ten year period but the proportion seeking medical assistance increased. Furthermore, there has probably been an increase in the number of visits to fertility clinics per couple in association with the increasing number of available treatments.

Reproductive medicine is a popular topic, and the media including magazines, newspapers, radio and television serve to inform the public of the advances in medical technology. Only fifty years ago treatment of infertility was relatively primitive. We have now reached a state where even with azospermia (absence of sperm in the man’s semen), it may be possible to aspirate (a needle is introduced into the scrotum) a few sperm and achieve fertilisation by intracytoplasmic sperm injection into the oocytes (eggs – Q10.25).

References:

Allocating fertility services by medical need (2001) 09-05-3368

Age, the desire to have a child and cumulative pregnancy rate (1997) 09-05-2001

Q 9. 6 What is the effect of our age on fertility?

Fertility declines with advancing female age. The prevalence of infertility reaches 25% in women in their late thirties and there is a rapid decline of fertility after the age of forty. There is also evidence of declining fertility with age in the male partner.

References:

The association of age and semen quality in healthy men (2003) (3571)

The effects of female age on fecundity and pregnancy outcome (2001) 09-06-3371

Effects of male age on semen quality and fertility: A review of the literature (2001) 09-06-3259

Human fertility does not decline: Evidence from Sweden. (1999) 09-06-2833

Age-related decline in fertility: A link to degenerative oocytes? (1997) 09-06-2006

The impact of the woman’s age on the success of standard and donor in vitro fertilization. (1997) 09-06-1694

Female age is an important parameter to predict treatment outcome in intracytoplasmic sperm injection. (1996) 09-06-2864

The age-related decline in female fecundity: A quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization (1996) 09-06-1911

Effect of age on sperm fertility potential: Oocyte donation as a model (1996) 09-06-1529

Delaying childbearing: Effect of age on fecundity and outcome of pregnancy (1991) 09-06-306

Q 9. 7 I smoke cigarettes. Can this have an effect on my fertility?

Cigarette smoking has an adverse effect on female and male fertility and smoking in pregnancy reduces the future fertility of the unborn child.

References:

Cigarette smoking and the risk of male factor subfertility: Minor association between cotinine in seminal plasma and semen morphology (2000) 09-07-3322

Smoking and female infertility: A systematic review and meta-analysis (1998) 09-07-2163

Does cigarette smoking impair natural or assisted fecundity? (1996) 09-07-1585

Reduced fecundability in women with prenatal exposure to cigarette smoking (1989) 09-07-960

Cigarette smoking associated with delayed conception (1985) 09-07-961

Q 9. 8 Does my weight influence fertility?

If you are overweight your fertility will be reduced. It is unclear whether it is the weight that is an independent factor or whether other factors such as polycystic ovary syndrome (PCOS – Q7.2) result in both the infertility and excess weight. At the other extreme, if you are under your ideal weight you are more likely to have anovulation problems (Q9.17). The Body Mass Index (BMI) is a ratio used to compare your weight with your height. The BMI is calculated as indicated in Table 9.1.

Table 9.1 Calculating your Body Mass Index.

BMI = Weight (Kg) / Height (m)2.

Your BMI should be between 20 and 24. If your BMI is less than 20 you are underweight. You should lose weight if your BMI is between 25 and 29. You are considered to be medically obese if your BMI is 30 or more and you would be regarded as very obese if your BMI is greater than 40.

Weight Kg &

(st / lb)

Height in metres & (ft ins)

Height (m2)

BMI

(7st 110lb)

1.63

(5ft 4ins)

1.632

18 (49 / 1.632 )

(9st 9lb)

1.58

(5ft 2ins)

1.582

24 (61 / 1.582 )

(14st 2lb)

1.68

(5ft 6ins)

1.682

32 (90 / 1.682)

106

(16st 10lb)

1.55

(5ft 1ins)

1.552

44 (106 / 1.552 )

Q9. 8A How can I lose weight?

Our body weight will remain steady if the amount of energy we obtain from our food is equal to the amount of energy we expend. If we take in more energy in the food that we eat than we burn up then we will gain weight and conversely if we burn up more energy than we obtain from our food then we will lose weight.

Energy is measured in calories. A calorie is the amount of energy required to raise the temperature of one millilitre of water by one degree centigrade. An average woman will use about 1800 to 2600 thousand calories each day. A kilocalorie (kcal) is a thousand calories. There appears to be a misquotation about the units of energy content of food. It is often said that a banana contains 100 calories. It contains 100 thousand calories (100 kcal).

As an approximate guide 400 kcals will equate to an ounce of body fat. Let us provide an example. A woman is keeping her weight steady and then changes habit and eats one less chocolate biscuit (100 kcals) each day. In one week, her calorie intake will be reduced by 700 kcal and in a 30 day month 100 x 30 = 3,000 kcals. As 400 kcals equates to an ounce of body fat, she would lose 3,000/400 = 7.5 ozs each month leading to a weight loss of 7.5 x 12 ozs = 90ozs or 90/16 = 5.6lbs in one year (2.5kgs).

The energy we burn in a day depends on our basal metabolic rate combined with the energy used as we work and exercise. Sadly, for those of us doing sedentary work, our brains do not consume additional energy even though they increase our mental output. The author may spend a lot of time working on his computer but this does not burn away calories.

Dieting and Exercise:

If we are honest with ourselves, most of us who have difficulty keeping our body weight down eat too much. There are clinical studies that have proven this. The simple answer to the question “How can I lose weight” is that you must consume less calories than you use. You can lose weight by reducing the amount of calories you eat in your diet and by increasing the amount of exercise that you undertake. Increasing your exercise is beneficial, not only because it increases your energy expenditure, but also because there will be an increase in proportion of muscle and this increases your basal metabolic rate.

There is some debate about the best form of diet to follow when weight loss is required. Carbohydrates, protein and fat each provide energy sources for the body and there has been an assumption that a carbohydrate calorie is equivalent to a protein or fat calorie. Most diets recommend reduction in total food intake and particularly of fat but there is an interesting deviation from this rule by a diet that strictly reduces carbohydrate intake whilst leaving virtual freedom in the amount of protein you eat (Atkins diet). From a theoretical point of view, it could be that reducing your carbohydrate intake and hence sugar absorption will reduce the amount of insulin released into the blood. Insulin converts sugar into body fat. Scientific studies are required to evaluate the relative benefits of these diets. Whichever diet you choose, a balanced diet with adequate vitamin requirements is essential for long-term health.

When you start a new weight reducing diet, do not be misled by dramatic changes in the first few days and weeks. A lot of food is present in the stomach and intestine. If you consume less food, the content of the intestine will be reduced leading to quick weight loss. If your basal metabolic rate is 2,500 kcals per day and you eat nothing then you would lose 2,500/400 (6.25) ozs of fat and serious problems can arise if you do not eat a sensible diet. If you were to keep to a 1500 kcal diet you would lose 1,000 kcals or 1000/400 (2.5ozs) per day or 75 ozs (4lb) in a month.

Clinical Causes of Body Weight Problems:

There are a few clinical situations that may confound the energy equation. The thyroid gland produces hormones such as thyroxine that set our basal metabolic rate – the rate that we consume energy at rest. Patients with an overactive thyroid have high levels of thyroxine and they tend to lose weight. Those with an under active thyroid will tend to gain weight.

In recent years, there has been an interest in ‘insulin resistance’ (Q7.3). Those with insulin resistance need to have increased levels of insulin to stop their blood sugar levels running to high. Insulin converts sugar into fat. This may explain why some patients with polycystic ovary syndrome tend to be obese (Q7.3). It does not explain why some patients who have PCOS are not overweight even though they have increased insulin resistance. Those who are obese and have PCOS may lose weight with a drug called metfomin (Q7.14).

Medical Treatment of Increased Body Weight:

Medical treatment, particularly with female hormones, is commonly blamed for weight increase and citation of medical texts used to justify these claims. These citations indicate that some patients gain weight on the treatment but they also say that others lose weight. Few of us are able to maintain a steady and desirable weight without watching our diet and most of us are in a state of weight loss or weight gain over the course of a few months. Most of us continue to gain weight at least until our fifties. Studies of body weight change with the combined oral contraceptive pill and with hormone replacement therapy have shown that overall there is no significant change in body weight attributable to them. There may be a redistribution of body fat with HRT; there could be an increase in breast tissue and reduction of the waistline.

Leptin is a hormone that regulates appetite and energy expenditure. Animals that are deficient in leptin tend to be obese. The majority of overweight people do not have leptin problems. Leptin can be manufactured and administered with the aim of causing weight loss. More needs to be known about the role of leptin before it could be considered as a potentially beneficial medication for the obese.

Orlistat (Xenical® – Roche) is a lipase inhibitor. Lipase is an enzyme that is secreted into the intestine to break down fat in our food. By reducing the lipase activity more fat passes through the intestine and is not absorbed. A potential problem with orlistat is that the stool may be greasy and some patients may report faecal incontinence at first. Appetite suppressing agents are not generally recommended for the obese as they tend to cause side effects. Diuretics are drugs that increase the amount of urine we produce and they reduce the amount of body fluid. They should not be used to reduce body weight.

Q 9. 9 I have fibroids. Could these reduce my fertility?

Fibroids (Q23.14) can be found in 50% of women. Many women with several large fibroids conceive without difficulty and go on to have uneventful pregnancies and deliveries. If you are found to have fibroids that are not affecting the cavity of the womb, they probably have no effect on your fertility. Uterine fibroids distorting the uterine cavity, however, may perhaps reduce the chance of pregnancy.

References:

Effect of uterine leiomyomata on the results of in-vitro fertilization treatment (1995) 09-09-952

Q 9. 10 I have been told that my womb has an abnormal shape and that was the way that I was born. Could this reduce my fertility?

During investigation of infertility, ultrasound examination or hysterosalpingography (Q9.20) may demonstrate a congenital abnormality of your womb (Q3.3). Many women with these abnormalities achieve pregnancy without difficulty and go on to have healthy babies.

References:

Clinical implications of uterine malformations and hysteroscopic treatment results. (2001) 09-10-3476

Uterine anomalies: How common are they, and what is their distribution among subtypes?. (1998) 09-10-3477

The role of hysteroscopy in unexplained infertility. (1997) 09-10-3479

Reproductive impact of congenital Mullerian anomalies. (1997) 09-10-3478

Q 9. 11 I have endometriosis. Could this reduce my fertility?

At times, tissue similar to the endometrium (lining of the uterus) may be found at other sites and this is called endometriosis (Q23.21).

Severe endometriosis is uncommon but undoubtedly it may damage the Fallopian tubes and ovaries resulting in infertility. The significance of milder forms of endometriosis as a cause of infertility, however, has been the subject of debate.

Endometriosis has been reported to be more common in infertile women although it is difficult to be certain because estimating the incidence of endometriosis in the general population must be subject to inaccuracy as the diagnosis requires an invasive procedure.

In women with primary infertility, mild endometriosis is more common when there is a male factor problems, suggesting that, in these women, infertility predisposes to endometriosis rather than the endometriosis being a cause for the infertility.

Mild endometriosis is extremely common: with scrutiny and appreciation of the various forms of lesions it can probably be found, at least intermittently, in the majority of women so that it should no longer be considered a pathological (disease) state. Treatment of mild endometriosis confers no improvement in pregnancy rates.

References:

Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility (1998) 09-11-2201

Using economics alongside medical audit. A case study of the management of endometriosis (1996) 09-11-2155

Buserelin acetate versus expectant management in the treatment of infertility associated with minimal or mild endometriosis: A randomized clinical trial (1992) 09-11-1036

The impact of treatment on the natural history of endometriosis (1990) 09-11-1030

The relationship between endometriosis and semen analysis: A review of 490 consecutive laparoscopies (1989) 09-11-1040

Successful treatment of asymptomatic endometriosis: does it benefit infertile women? (1987) 09-11-980

Q 9. 12 I have been told that I have cervicitis or a cervical ectopy (erosion). Could this impair my fertility?

Cervicitis and cervical ectopy (Q21.3) are frequently found at the time of taking a cervical smear test. There is no evidence that either reduce fertility.

Q 9. 1 What is infertility?

Q 9. 2 How common are infertility problems?

Q 9. 3 What are the main causes of infertility?

Q 9. 4 What are the objectives of our infertility investigations?

Q 9. 5 Have there been any noticeable changes in fertility requirements in recent years?

Q 9. 6 What is the effect of our age on fertility?

Q 9. 7 I smoke cigarettes. Can this have an effect on my fertility?

Q 9. 8 Does my weight influence fertility?

Q9. 8A How can I lose weight?

Q 9. 9 I have fibroids. Could these reduce my fertility?

Q 9. 10 I have been told that my womb has an abnormal shape and that was the way that I was born. Could this reduce my fertility?

Q 9. 11 I have endometriosis. Could this reduce my fertility?

Q 9. 12 I have been told that I have cervicitis or a cervical ectopy (erosion). Could this impair my fertility?

Q 9. 13 My doctor tells me that my womb is retroverted (tilts backwards). Could this reduce my fertility?

Q 9. 14 I have had an ectopic pregnancy. Does this affect my future fertility?

Q 9. 15 We are worried that we may have a fertility problem. What should we do?

Q 9. 16 How will our doctor be able to identify the cause of our infertility?

Q 9. 17 How can we tell if I am releasing my eggs (ovulating)?

Q 9. 18 Investigations have shown that I have a problem releasing my eggs (anovulation). What could be the cause of this?

Q 9. 19 How important are my Fallopian tubes in fertility?

Q 9. 20 How can we tell if my Fallopian tubes are functioning?

Q 9. 21 How can we assess male fertility?

Q 9. 22 What is the purpose of a post-coital test (PCT)?

Q 9. 23 We have had our infertility investigations and our problem remains unexplained. How can this be?

Q 9. 24 What are our chances of achieving a pregnancy?

Q 9. 25 Where can I obtain more information?

Q 9. 26 Could I have some useful Web sites?

Women’s Health – Home Page

Q9. 13 My doctor tells me that my womb is retroverted (tilts backwards). Could this reduce my fertility?

About one lady in five has a womb that tilts backwards (Q23.27). At one time it was believed that a retroverted womb was associated with virtually every kind of gynaecological symptom, including infertility, and an operation called ventrosuspension was performed to tilt the womb forward. It is now recognised that women with retroverted wombs are no less fertile than those with an anteverted (forward tilting) uterus and surgery is not beneficial.

References:

The timing of the ‘fertile window’ in the menstrual cycle: Day specific estimates from a prospective study (2000) 09-13-3364

Q 9. 14 I have had an ectopic pregnancy. Does this affect my future fertility?

A history of ectopic pregnancy would increase your chance of infertility in the future. If you do conceive there is a one in thirty chance of another ectopic pregnancy. It would be advisable for you to have a series of ultrasound scans in your next pregnancy to check that this time the pregnancy is within the uterus.

References:

Survival analysis of fertility after ectopic pregnancy (2001) 09-14-3252

Ectopic pregnancy and infertility following treatment of infertile couples: A follow-up of 929 cases (1991) 09-14-1066

Q 9. 15 We are worried that we may have a fertility problem. When should we seek infertility investigation?

Your general practitioner will be able to advise you and may be able to initiate infertility investigation. The results may influence how you proceed. Infertility investigations are usually commenced if pregnancy has not occurred within a year. It would be appropriate to commence infertility investigations and treatment earlier if you have an abnormal menstrual cycle, a history suggesting possible tubal disease, coital difficulties or if you have had infertility problems before. A semen test would indicate if there is a male factor to the infertility.

Rubella (German Measles), which can damage the fetus in pregnancy, is avoidable by ensuring adequate immunity and infertility investigation provides us with an opportunity to ensure that you are immune. If a blood test shows that you have inadequate immunity, your general practitioner will arrange for you to be immunised.

Q 9. 16 How will our doctor be able to identify the cause of our infertility?

Initially your doctor will wish to obtain a full history of the problem, examine you and start some investigations. Figure 9.2 is a flowchart outlining how infertility can be investigated and treated.

References:

Optimal use of infertility diagnostic tests and treatments. (2000) 09-16-3037

Practice patterns among reproductive endocrinologists: Further aspects of the infertility evaluation (1998) 09-16-2215

Q 9. 17 How can we tell if I am releasing my eggs (ovulating)?

If you are seeing your periods on a reasonably regular monthly cycle, without hormone treatment, there is a very good chance that you are ovulating; a regular cycle does not, however, guarantee this. No test, other than a positive pregnancy test, can provide absolute evidence that you have ovulated.

• Anovulatory (eggs are not being released) infertility is suggested by amenorrhoea (absent periods – Q6.1), oligomenorrhoea (infrequent periods – Q6.2) or irregular menstruation.

• Many women experience a change in their vaginal discharge just before ovulation, the mucus becoming more watery and stretchy. Mid-cycle pelvic pain usually indicates ovulation.

• A basal temperature chart provides a simple and inexpensive early indication of ovulation. The temperature can be taken by mouth with a regular thermometer that should be easy to read. The clinic nurse can teach you how to use this instrument. The temperature should be taken before the day’s activity begins. Typically, the temperature falls and then rises by 0.5 degrees centigrade around the time of ovulation. Sexual intercourse should be recorded on the chart as this may show that timing of intercourse may be inappropriate in relation to ovulation. The temperature remains elevated through the luteal phase (second half of the cycle) as a marker of progesterone activity (Fig.2.3). The rise of the temperature in association with ovulation is apparent only retrospectively and couples should appreciate that it is not a useful predictor of imminent ovulation. A sustained elevation of the temperature in association with failure to menstruate is usually diagnostic for pregnancy. The popularity of the temperature chart has fallen as other tests seem more accurate.

• Home testing for the LH surge (Q2.14; 6.11) provides a valuable method for determining the timing of ovulation, potentially reducing stress and costs of fertility treatments. These ovulation predictor tests are available from your local chemist.

• A blood test for progesterone level is a useful guide to ovulation. The test should be taken between four and ten days before a period (day 21 is perfect for a 28 day cycle). A result in excess of 30 nmol/l is generally accepted as evidence of ovulation. There is a suggestion that slightly higher levels of progesterone should occur in patients taking clomiphene or tamoxifen.

• Ultrasound (Q4.9) has found an important role in the investigation and treatment of infertility. An initial single ultrasound evaluation of the pelvis on the twelfth day of your cycle provides a useful assessment of your ovaries and uterus. At this time there should be a dominant follicle of at least 12 mm in a twenty eight day cycle and the endometrium should be well developed with adequate oestrogenic activity. A series of ultrasound examinations (follicle tracking scans) from about the sixth day of your cycle will chart egg (follicular) development and release.

References:

Home ovulation testing in a donor insemination service (1996) 09-17-2161

[Value of the Clearplan Ovulation Test in sterility treatment]. German 09-17-992

Plasma progesterone levels as an index of ovulation (1983) 09-17-1019

The value of a single serum progesterone measurement in the midluteal phase as a criterion of a potentially fertile cycle (“ovulation”) derived form treated and untreated conception cycles (1982) 09-17-1018

Problems in using basal body temperature recordings in an infertility clinic (1977) 09-17-705

Q 9. 18 Investigations have shown that I have a problem releasing my eggs (anovulation). What could be the cause of this?

Failure of ovulation (anovulation) is the cause of infertility in 20 – 25% of couples referred to an infertility clinic. Anovulation may be associated with:

• amenorrhoea (absent periods – Q6.1) – a successful outcome to treatment can be expected in 95% of patients with infertility.

• oligomenorrhoea (infrequent periods – Q6.2). – a successful outcome to treatment can be expected in 75% of patients with infertility.

• normal menstrual cycles – there may be evidence of ovulatory problems detectable on ultrasound or serum progesterone levels.

• polycystic ovary syndrome (Q7.2) – the most common reason for anovulation.

• hyperprolactinaemia (high prolactin levels) – diagnosed when the prolactin level is inappropriately elevated (Q6.10). Prolactin (Q6.10) is the hormone responsible for milk production after childbirth. Breast feeding mothers tend not to see their periods quite as quickly as non-breast feeding mothers as a result of the increased prolactin levels. This is probably nature’s way of providing some spacing between pregnancies. In mild hyperprolactinaemia there may be reduced frequency of periods whereas in severe cases there may be amenorrhoea(Q6.4). Galactorrhoea (inappropriate lactation – Q6.10) is a symptom indicative of hyperprolactinaemia (Q6.10). Ovulatory disorders may be a manifestation of hyperprolactinaemia. Prolactin levels may be slightly elevated in patients with polycystic ovary syndrome and hypothyroidism. Higher levels may be found with pituitary adenomas (tumours) and radiological examination of the pituitary fossa is indicated. Routine prolactin measurement in women with normal menstrual cycles is probably of no value.

• premature menopause (Q6.17; 26.1) is indicated by cessation of menstruation and repeatedly elevated FSH levels (Q2.14 – >30IU/L). In the years leading up to the menopause, FSH levels tend to gradually rise.

• the ‘inadequate luteal phase’ is a loose term that has been the subject of an inconsistent definition and recognition. A shortened luteal phase (Q9.17), borderline progesterone estimations (Q9.17), and reduced hormonal effects on histological (microscopic) assessment of the endometrium have all been cited as diagnostic features.

References:

Is glycosylated haemoglobin a marker of fertility? A follow-up study of first-pregnancy planners. (1999) 09-18-3041

The significance of FSH elevation in young women with disorders of ovulation (1980) 09-18-697

Q 9. 19 How important are my Fallopian tubes in fertility?

Your Fallopian tubes have four functions:

• They must be able to pick up the ova (eggs) from the ovaries.

• It is in the Fallopian tubes that ova are fertilised by spermatozoa.

• The tubes actively transport the ova to the uterine cavity by the coordinated action of tiny fine hair-like structures called cilia.

• During their passage along the tubes, ova are nourished.

Approximately 14% of infertility is attributable to the “tubal factor”. Infection ascending to the Fallopian tubes following pregnancy or through sexual transmission accounts for the majority of patients with Fallopian tube problems (pelvic inflammatory disease – Q20.2).

References:

Bacterial vaginosis and past chlamydial infection are strongly and independently associated with tubal infertility but do not affect in vitro fertilization success rates. (1999) 09-19-2895

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: A surprising result? (1994) 09-19-506

Q 9. 20 How can we tell if my Fallopian tubes are functioning?

Tubal function tests generally provide evidence of patency only. The earliest work on the subject was published in 1920 when it was demonstrated that if the tubes are patent, oxygen introduced through the cervix would pass into the peritoneal cavity. The concept that investigation of tubal patency may be therapeutic (increase the likelihood of pregnancy) also dates from about that time. In the 1940s hysterosalpingography (HSG) was introduced. A radio-opaque dye was introduced through the cervix and an x-ray picture was taken to track the dye through the uterus and Fallopian tubes (Figure 9.3).

The arrival of fibroptic light technology and the first reports of the laparoscope (Q23.24) into the English literature opened the world of direct visualisation of the pelvic organs. When combined with methylene blue dye insufflation (the dye is passed through the cervix), a new technique for assessing tubal patency became available (laparoscopy with dye insufflation). Often hysterosalpingography and laparoscopy provide differing evidence on tubal patency.

In 1984, ultrasound assessment of the Fallopian tubes (hysterosalpingo-contrast-sonography – Hy-Co-Sy) was first reported to demonstrate free fluid in the pelvis after introducing fluid through the cervix; there was good correlation with hysterosalpingography in a series of 35 infertile women.

Current routine techniques for the evaluation of the tubal factor are basically patency tests; they do not assess other functions such as the ability of the fimbria (Q2.3) to pick up the oocytes or move them along to the uterus. There have been reports of evaluation of Fallopian tube function by introducing starch suspensions, vaseline droplets and Indigo Carmen into the pelvis and checking to see if the tubes pick these up and transport them into the uterus by looking to see if they appear at the cervix some hours later. These tests never progressed beyond the realms of research.

In a study of 104 infertile couples, the women had both hysterosalpingography and laparoscopy with dye insufflation. There was an overall agreement between the two techniques in 62.5% of cases. It was concluded that whenever the HSG demonstrated tubal patency with free flow of dye, laparoscopic may not be necessary. At one time it was argued that laparoscopy had the advantage as it would allow a diagnosis of minimal endometriosis. This no longer seems relevant as such findings are of no clinical relevance (Q9.11). Several experts have come to the conclusion that in the absence of clinical indicators of significant pelvic disease and a normal hysterosalpingogram there is little to be gained by submitting infertile women to laparoscopy.

Bibliography:

Investigation of the infertile couple: should diagnostic laparoscopy be performed after normal hysterosalpingography in treating infertility suspected to be of unknown origin? (2002) 3490

Technical results of falloposcopy for infertility diagnosis in a large multicentre study (2001) 09-20-3266

Cost-effectiveness of hysterosalpingography, laparoscopy, and Chlamydia antibody testing in subfertile couples (2001) 09-20-3253

Comparison of hysterosalpingography and laparoscopy in predicting fertility outcome. (1999) 09-20- 2699

Evaluation of the performance of hysterosalpingo contrast sonography in 500 consecutive, unselected, infertile women (1998) 09-20-2165

A randomized study comparing air to Echovist(TM) as a contrast medium in the assessment of tubal patency in infertile women using transvaginal salpingosonography (1997) 09-20-2061

Is routine diagnostic laparoscopy for infertility still justified? A pilot study assessing the use of hysterosalpingo-contrast sonography and magnetic resonance imaging (1997) 09-20-1845

Is hysterosalpingography an important tool in predicting fertility outcome? (1997) 09-20-1692

Accuracy of hysterosalpingography and laparoscopic hydrotubation in diagnosis of tubal patency (1995) 09-20-710

[Falloposcopy–a new method for evaluation and treatment of infertility due to tubal factors]. Hebrew 09-20-990

Color Doppler ultrasonography assessment of tubal patency: A comparison study with traditional techniques (1992) 09-20-999

Echohysterosalpingography: New diagnostic possibilities with S HU 450 Echovist (1991) 09-20-1073

Investigation of tubal infertility by radionuclide migration (1991) 09-20-984

Fallopian tubal patency assessed by ultrasound following fluid injection. Work in progress (1984) 09-20-1072

The alleviation of uterocornual spasm of the Fallopian tubes during hysterosalpingography by intravenous administration of orciprenaline (1976) 09-20-982

Q 9. 21 How can we assess male fertility?

Male factor problems account for at least 30% of infertility. A story of mumps in adult life may indicate the possibility of problems but most male factor problems are identified from microscopic assessment of a fresh semen sample (semen analysis / male fertility test).

The volume of semen produced at ejaculation should be greater than 1ml. There is debate about the minimum concentration of healthy motile (freely moving) sperm required to achieve pregnancy. The count varies according to frequency of intercourse and from day to day. As an approximate guide, there should be at least three million actively motile sperm per ml.

As an example, a semen sample has a volume of 2mls – this is normal. There is a count of 30 million sperm per ml and 33% are motile – total motile count is 10 million. Of these, 50% are actively motile – actively motile count is 5 million per ml and the result is normal.

References:

Preoperative semen analysis as a predictor of seminal improvement following varicocelectomy (2001) 09-21-3257

Effect of the total motile sperm count on the efficacy and cost-effectiveness of intrauterine insemination and in vitro fertilization (2001) 09-21-3294

Q 9. 22 What is the purpose of a post-coital test (PCT)?

A post-coital test involves taking a sample of the mucus from the cervical canal between eight and twelve hours after intercourse around the time of ovulation (days 13-14 in a 28 day cycle). The mucus is placed on a glass slide and then examined under a microscope. You should have the opportunity of looking down the microscope for yourselves.

There is debate as to the value of the test. A positive test will show reasonable numbers of actively motile sperm and confirms that ovulation is taking place, that the male partner is producing reasonable quality sperm and that the mucus is not inhibiting sperm movement. A positive test also confirms that intercourse is resulting in semen being deposited on the cervix.

It has been estimated that 6% of infertility is related to coital difficulties and it seems entirely appropriate to me that this should be checked by such a simple test particularly as other fertility tests and treatment can be expensive. The cervical mucus may be hostile to sperm even during ovulation and cervical factor has been considered to be responsible in up to 10% of couples presenting with infertility. Whilst a positive test is reassuring, a negative test is more difficult to evaluate. On several occasions we have seen a negative test in a conception cycle. Another argument against the post-coital test is that the most common form of treatment, whether the test is positive or not, is intrauterine insemination (Q10.23).

The majority of our patients find it reassuring to know that this potential cause for otherwise unexplained infertility has been checked. There are occasions when the post-coital test identifies an unexpected coital problem. The test may be of greater value in units that use treatments specifically for the cervical factor such as pre-ovulatory oestrogen or pre-coital sodium bicarbonate douching (Q10.22)

In vitro cross testing, utilizing donor mucus and sperm can indicate the origin of an abnormal PCT. A drop of the partner’s sperm and donor sperm are placed on a glass slide in contact with the woman’s cervical mucus and also with donor mucus from another woman. Penetration of the mucus is evaluated microscopically. These tests have become less popular now that we have more advanced treatments.

References:

Predicting conception. 09-22-3524

When is the post-coital test normal? A critical appraisal (1995) 09-22-729

European postcoital tests: opinions and practice (1995) 09-22-728

The validity of the postcoital test for estimating the probability of conceiving. (1994) 09-22-2863

Prognostic value of the postcoital test: prospective study based on time-specific conception rates (1982) 09-22-739

Q 9. 23 We have had our infertility investigations and our problem remains unexplained. How can this be?

“Unexplained infertility” is an arbitrary diagnosis derived by exclusion according to the protocols of the investigating department. It may be frustrating for an infertile couple concluding their initial set of infertility investigations to learn that no explanation has been detected. We try to take a more positive attitude on the situation, for eventual success is more likely, even with low-tech treatment, than when infertility is attributable to male factor or tubal factor. The average spontaneous pregnancy rate with unexplained infertility over three years is 60%.

We regard infertility as being unexplained if there is a normal semen analysis, reasonable follicular development (>12mm) on the twelfth day of the menstrual cycle and a mid-luteal progesterone of at least 30 nmol/l, a normal hysterosalpingogram and a positive post-coital test. Depending on the criteria employed, it is believed that infertility cannot be explained for between 10% and 25% of couples.

Recurrent failure of implantation of an embryo in some women suggests that the endometrium may be an infertility factor. Immunological differences between the endometrium of women with unexplained infertility compared to fertile women has led to the suggestion that this could account for some cases of unexplained infertility. Antiphospholipid antibodies (Q12.17), notably lupus anticoagulant and anticardiolipin, are more prevalent in women with unexplained infertility. It may be that we should consider investigating prolonged unexplained infertility with antiphospholipid antibody studies and chromosome analysis but this approach has not been widely adopted.

Arguably the most significant cause of infertility is implantation failure. From a practical point of view, the next area for significant development in the treatment of infertility lies in our understanding of embryo implantation. Only 12% of embryos transferred during IVF result in a live birth although implantation is probably around 25% in natural conception. Further research is required to improve our understanding in this critical area of fertility investigation but successful treatment for implantation problems remains elusive.

A successful outcome of assisted fertility treatment is reduced to about 30% in women over forty which contrasts to 50% in younger women. The reduction in fertility with age could be related to oocytes or to uterine factors.

References:

Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis. (2000) 09-23-3219

The interaction of parameters of male and female fertility in couples with previously unexplained infertility (1990) 09-23-1061

Q 9. 24 What are our chances of achieving a pregnancy?

It is impossible to give an accurate prognosis. Some couples who seem to have everything going against them succeed whereas others who seem to have a good prognosis do not. Several specialists have suggested formulae to provide some assistance in answering this central question. We have devised the following formula:

Prognostic Fertility Index = [50- Female Partner Age] x Male Factor x Tubal Factor

/ Years of Infertility

The Male factor is the number of millions of actively motile sperm per ml of semen

(Maximum = 5)

The Tubal Factor is assessed as follows:

5 – No known tubal disease.

4 – History of pelvic inflammatory disease – both tubes patent.

3 – One tube patent and one blocked.

2 – One tube removed (e.g. for ectopic pregnancy) and

the other tube patent.

1 – Both tubes blocked.

0 – Both tubes have been removed.

The number of years is calculated counting the current year as one. For examples:

trying for less than one year = 1.

trying for two years and six months = 3.

Our index does not include ovulation as ovulation induction treatment can usually overcome most ovulatory problems.

Examples of calculating the Prognostic Fertility Index are provided in Table 9.2.

Table 9.2 Examples of calculations of the Prognostic Fertility Index.

Age (Female)

Male Factor (Q9.21)

Tubal Factor

Years of Infertility

Prognostic Fertility Index

2 1/2

208 ( [50-25] x 5 x 5 /3 )

67.5 ( [50-35] x 3 x3 / 2 )

3 ( [50-46] x 2 x2 / 5 )

With few exceptions, a Prognostic Fertility Index of less than 30 carries a poor chance of success without IVF.

References:

Evaluation of pregnancy rates after intrauterine insemination according to indication, age, and sperm parameters. (1998) 09-24-2878

First and subsequent pregnancies after tubal microsurgery: Evaluation of the fertility index. (1997) 09-24-2880

Prognosis for fertility analyzing different variables in men and women. (1996) 09-24-2882

Score prognosis for the infertile couple based on historical factors and sperm analysis. (1994) 09-24-2881

Fertility prognosis for infertile couples. (1993) 09-24-2861

Age of the female partner is a prognostic factor in prolonged unexplained infertility: A multicentre study. (1989) 09-24-2850

Duration of involuntary infertility and subsequent pregnancy. (1987) 09-24-2800

Simple model and empirical method for the estimation of spontaneous pregnancies in couples consulting for infertility. (1987) 09-24-2799

Q 9. 25 Where can I obtain more information?

American Infertility Association

Q 9. 26 Could I have some useful Web sites?

Evaluation of the quality of Web sites is discussed in Q4.27. You may find that several general women’s health sites may help you (Q4.28). The following are more specialised Web sites on topics found in this chapter:-

This page was last updated:-19-Jun-2002

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Q 9. 1 What is infertility?

References:

Q 9. 2 How common are infertility problems?

References:

Q 9. 3 What are the main causes of infertility?

References:

Q 9. 4 What are the objectives of our infertility investigations?

Q 9. 5 Have there been any noticeable changes in fertility requirements in recent years?

References:

Q 9. 6 What is the effect of our age on fertility?

References:

Q 9. 7 I smoke cigarettes. Can this have an effect on my fertility?

References:

Q 9. 8 Does my weight influence fertility?

Q9. 8A How can I lose weight?

Dieting and Exercise:

Q 9. 9 I have fibroids. Could these reduce my fertility?

References:

Q 9. 10 I have been told that my womb has an abnormal shape and that was the way that I was born. Could this reduce my fertility?

References:

Q 9. 11 I have endometriosis. Could this reduce my fertility?

References:

Q 9. 12 I have been told that I have cervicitis or a cervical ectopy (erosion). Could this impair my fertility?

Q9. 13 My doctor tells me that my womb is retroverted (tilts backwards). Could this reduce my fertility?

References:

Q 9. 14 I have had an ectopic pregnancy. Does this affect my future fertility?

References:

Q 9. 15 We are worried that we may have a fertility problem. When should we seek infertility investigation?

Q 9. 16 How will our doctor be able to identify the cause of our infertility?

References:

Q 9. 17 How can we tell if I am releasing my eggs (ovulating)?

References:

Q 9. 18 Investigations have shown that I have a problem releasing my eggs (anovulation). What could be the cause of this?

References:

Q 9. 19 How important are my Fallopian tubes in fertility?

References:

Q 9. 20 How can we tell if my Fallopian tubes are functioning?

Bibliography:

Q 9. 21 How can we assess male fertility?

References:

Q 9. 22 What is the purpose of a post-coital test (PCT)?

References:

Q 9. 23 We have had our infertility investigations and our problem remains unexplained. How can this be?

References:

Q 9. 24 What are our chances of achieving a pregnancy?

References:

Q 9. 25 Where can I obtain more information?

Q 9. 26 Could I have some useful Web sites?

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