Fecundity

Infertility is the inability of a couple to conceive after 1 year of sexual intercourse without using any type of contraception. Fecundity indicates the rate of conception occurring in a population in a given time period, usually 1 month. In clinical practice infertility is usually defined as a failure to become pregnant during a 12-month period of regular unprotected intercourse. Each couple has a more or less constant monthly probability of conceiving, but between couples the probabilities vary widely, from 0 per cent (3-5 per cent of couples) to an upper limit of about 60 per cent. Up to 25 per cent of all women attempting to conceive had an episode of subfertility defined as 1 year failure to conceive with regular unprotected intercourse or the occurrence of more than two spontaneous miscarriages or stillbirths at some time in their reproductive life. Three per cent of all women aged 25-44 were found to be involuntarily childless and 6 per cent of parous women were not able to have as many children as they wished.

As the duration of inability to achieve a pregnancy increases, the probability of success during the subsequent year sharply decreases. However, if the period of infertility is short (12 months) there is a 50 per cent chance of conception in the subsequent year. Therefore, depending on the cause of infertility, it may be useful to wait rather than pursue assisted reproductive techniques  early in the period of infertility.

Infertility and age.

Infertility risk correlates with age as follows:

  • ■  30-34, 1 in 7
  • ■  35-40, 1 in 5
  • ■  40-44, 1 in 4.

For couples who stop using contraception in order to conceive, only 50 per cent conceive in 3 months, 75 per cent in 6 months and 90 per cent by 1 year.

Table  Infertility and age.

Age Risk of never having a child (%)
20-24 6
25-29 9
30-34 15
35-40 30
40-44 64

After 2 years of trying to conceive, about 5 per cent of original couples will not have conceived. To determine that any treatment of infertility is superior to no treatment, statistical analysis of the effect of treatment on the incidence of pregnancy over time needs to be calculated.

The human ovum is capable of being fertilised for only about 24 hours after ovulation. Spermatozoa retain their fertilising ability for about 48 hours after intercourse. Ovulation usually occurs 12-16 days (14 ± 2 days) before the onset of the subsequent menses. The egg is fertilised within a few hours after it reaches the ampulla of the oviduct. It is best that sperm are present when the egg arrives so that fertilisation can occur. Intercourse should occur before ovulation for maximal likelihood of pregnancy. Pregnancy therefore can arise from day 8 (likelihood of pregnancy is 8 per cent) until day 14, the day of ovulation (likelihood is 36 per cent). Pregnancy does not occur after ovulation or more than 6 days before ovulation based on studies done on a single act of sexual intercourse and pregnancy rates. Because ovulation is sometimes inaccurately determined, the advice is that intercourse should not be timed, but should occur regularly throughout the cycle. Sperm transport to the oviduct from the cervix normally occurs from 5 minutes to 5 days after intercourse. Ovulation occurs 1-3 days after the basal body temperature nadir and 1 day after the luteinising hormone  peak. There is only a 20 per cent chance of conceiving in each ovulatory cycle even with optimally timed intercourse.

Conception

The greatest possibility of conception is in the 2 days before ovulation and the day of ovulation itself. Semen quality measured in terms of motility and morphology declines with more than 10 days’ abstinence. Regular intercourse – two to three times a week – should ensure that it falls within the fertile period.

Change in cervical mucus is a good indicator of the fertile period. After menstruation there are a variable number of days where there is no vaginal loss of mucus. The change in cervical mucus correlates well with the fertile period. The onset of the fertile mucus is characterised by the appearance of increasing quantities of ‘cloudy’ or sticky secretion. The sensation is one of dampness. In the immediate pre-ovulatory period the mucus is clear, slippery, lubricative and stringy like raw egg white. The last day of the presence of this mucus is the ‘peak symptom’ indicating the maximal day of fertility (1 day before the luteinising hormone surge). After ovulation, the mucus becomes thick, tacky, opaque and diminished in volume. Basal body temperature charts are poor predictors of the day of ovulation and are not indicated in clinical practice. Luteinising hormone detection kits may be better at detecting the onset of the luteinising hormone surge, but there is no evidence that using the detection of the luteinising hormone surge improves the conception rate.

A midluteal serum progesterone estimation is proof of ovulation at a value of 30 nmol/1. Up to 9 per cent of regular menstrual cycles (defined by the World Health Organisation (WHO) as a cycle length of 25-35 days) are thought to be anovulatory. If the woman has a long or unpredictable cycle the sample may need to be performed later in the cycle than day 21 (e.g. day 28 for a regular 35-day cycle), or be repeated weekly until the next menstrual cycle starts.

Prognosis

Prognosis in infertility treatment (likelihood of pregnancy) generally is inversely related to the time spent trying to conceive. For unexplained infertility, In vitro fertilisation is indicated after 3 years of trying.

Lifestyle modification with infertility

■ Both partners should stop smoking. Smoking is detrimental to fertility [8]. Infertile women should be advised to stop smoking to enhance their fecundity and reduce the risk of miscarriage and growth retardation in the fetus. Fertilisation rates in smokers are one third that of normal couples with assisted reproductive techniques. Smoking affects sperm quality adversely.

■  Alcohol intake should be limited to one to two units once or twice a week. Women trying to become pregnant or at any stage of pregnancy should drink no more than one or two units twice a week.

■  Body mass index (BMI = weight (kg)/height (m)2) ideally should be in the normal range [11]. The internationally accepted range for BMI is: underweight <18.5, normal 18.5-24.9, overweight 25.0-29.0, obesity 30.0-39.9, extreme obesity >40. Underweight women (BMI <20kg/m2 or <47kg) are frequently hypo-oestrogenic and anovula-tory. Similarly overweight women are often anovulatory particularly with polycystic ovary syndrome. BMI should be not greater than 30. Fat needs to comprise at least 22 per cent of body weight. Short-term weight reduction, even for a period of 6 months, is often effective in restoring ovulation. Calorie restriction of itself may be more important than the actual weight loss.

■  Male partners should be advised to limit their drinking. Men with poor quality sperm should be advised to wear loose-fitting underwear and trousers and avoid occupational or social situations that might cause testicular hyperthermia. Hyperthermia does have a detrimental effect on sperm quality. This may be important in terms of fertility outcome if the man already has suboptimal semen parameters. Advising loose-fitting underwear and trousers is a simple, effective intervention.

■  Advise 0.4 mg folic acid as a supplement to take when trying to conceive and during the first 12 weeks of pregnancy in order to prevent neural tube defects. The dose should be increased to 4mg daily in women who have previously had a baby with a neural tube defect, or those taking medication, or with epilepsy and in recurrent miscarriage.

■  Advice should be given concerning risk in any subsequent pregnancy both of the technique and the pregnancy in a relative way.

Investigations of infertility

Female partner

■  Rubella status: If it is negative, rubella vaccination should be offered and the woman advised not to become pregnant within 1 month of immunisation.

■  Thyroid function tests should be done in infertile women with irregular menstrual cycles and in women with signs or symptoms of thyroid disease.

■  Prolactin levels should only be done in those women with amen-orrhoea, oligomenorrhoea or clinical symptoms of hyperprolacti-naemia such as galactorrhoea.

Table  Risks for counselling for infertility treatment. Risks related to pregnancy outcome

Event Material risk
Miscarriage 1 in 7
Premature birth 1 in 15
Birth defect in the baby 1 in 20
Death of the baby 1 in 100
Cerebral palsy in the baby 1 in 400
Death of the mother 1 in 14000

Material risks related to a woman’s age

Age (years) Chance of death in 1 year when otherwise fit and healthy
40 1 in 1000
50 1 in 500
60 1 in 170
Women aged 50 years, no family history, chance of developing breast carcinoma in the next 12 months 1 in 500
Ovarian carcinoma 1 in 90

‘Life risks’

Activity Chance of death in 1 year
Driving a car 1 in 6000
Motorcycling 1 in 1000
Continuing pregnancy 1 in 14000
Laparoscopy 1 in 67000
Termination of pregnancy 1 in 500000
Jumbo jet flight 1 in 2000000

■ Evidence of ovulation: measure follicle-stimulating hormone and luteinising hormone levels on days 3-5 of the cycle together with oestradiol levels; if these are high they produce a negative feedback effect on follicle-stimulating hormone levels. High follicle-stimulating hormone levels are inversely proportional to the ability to get pregnant.

Table Factors which influence infertility.

Duration of infertility
Age of the woman
BMI in the female partner
History of male urethritis
Percentage of motile spermatozoa
Quality of motility
Motile sperm concentration
Total motile sperm
Sperm morphology
Sociodemographic factors
Male profession
Alcohol consumption
Sauna bathing
Physical exercise
Mumps
Orchitis
History of prostatitis
Smoking
Coital frequency
Conception rate decreases by 15% per 1 year’s duration of infertility and by up to 3% per year of the female partner’s increasing age

Table Causes of infertility.

Anovulation 10-15%
Pelvic factors – adhesions from endometriosis or infection or tubal occlusion 30-40%
Abnormalities in male reproductive system – oligozoospermia, high viscosity of semen, low sperm motility, or low volume of semen (male factor) 30-40%
Abnormal sperm-cervical mucus penetration (cervical factor) 5%
Unexplained infertility 10-25%

This is particularly significant in the older woman where higher follicle-stimulating hormone levels suggest a poorer response of the ovary to novulation induction agents.

■ A  serum progesterone of >20IU/1  on day 21  is indicative of ovulation.

Table Initial investigations for infertility.

Follicle-stimulating hormone should be less than 3-5IU/I in the early follicular phase of the cycle. If elevated it is a useful indicator that the woman’s ovarian age is more advanced than her chronological age. Check on oestradiol at the same time because a level >250pmol/l will cause a decrease in the follicle-stimulating hormone by negative feedback
Fasting blood glucose – serum progesterone in the mid-luteal phase (5-7 days after the basal body temperature shift)
Chlamydia – IgG antibodies to Chlamydia trachomatis – if positive, indicates possible tubal adhesions
Thyroid function tests
Pelvic ultrasound
Prolactin if amenorrhoeic
Semen analysis
Hysterosalpingography in the follicular phase of the cycle

Table  Ovulation disorders.

(1) Intrinsic ovarian failure: genetic, autoimmune, others, e.g. cytotoxic chemotherapy
(2) Secondary ovarian dysfunction
(a) disorders of gonadotrophin regulation
(i) specific hyperprolactinaemia, Kallmann’s syndrome (WHO group I)
(ii) functional (WHO group I): weight loss, exercise, drugs, idiopathic
(b) gonadotrophin deficiency (WHO group I): pituitary tumour, pituitary necrosis or thrombosis
(c) disorders of gonadotrophin action (WHO group II): polycystic ovary syndrome

■  Test tubal patency: a hysterosalpingogram may be used as a screening test for tubal patency in a low risk couple. When an evaluation of the pelvis is indicated a diagnostic laparoscopy with dye insufflation should be done. Screen women for Chlamydia trachomatis and give antibiotic prophylaxis if positive. If detected, partners should be treated. Fallopian tube obstruction is found among 20-33 per cent of infertile couples. It may occur without any history of significant physical findings.

■  Hysterosalpingography gives information about the uterine cavity and isthmus of the tube, that laparoscopy and dye cannot provide. Laparoscopy gives  information  about  the presence  of peritubal adhesions, endometriosis and ovarian pathology.

Table Causes of secondary amenorrhoea (0.8% of general population).

1 Uterine
Normal endocrine function
Intrauterine adhesions (previous evacuation, curettage)
Obliteration of the uterine cavity
Endometrial destruction
Previous endometritis or fibrosis following myomectomy, metroplasty,
Caesarean section
Diagnosis – pass uterine sound
2 Polycystic ovary syndrome
Elevated luteinising hormone levels
Elevated androgen levels
Functional hypothalamic amenorrhoea
3 CNS hypothalamic causes
Interference with gonadotrophin-releasing hormone (gonadotropin-releasing hormone) release
Craniopharyngiomas, granulomatous disease (tuberculosis and sarcoidosis), encephalitis
4 Pituitary causes
Non-neoplastic lesions – damage of pituitary cells due to anoxia, thrombosis or haemorrhage
Sheehan’s syndrome – hypotensive episode in pregnancy
5 Drugs
Phenothiazines
Antihypertensive agents
6 Stress and exercise
Mechanism: low adipose tissue shifts the pathway of oestrogen metabolism towards 16-hydroxylation, forming catechol oestrogens. The competition between catecholamine and catechol oestrogens for catechol-O-methyltransferase may increase dopamine levels which in turn suppress the release of gonadotropin-releasing hormone and hence luteinising hormone.
7 Weight loss
Mechanism due to failure of normal gonadotropin-releasing hormone release
Anorexia nervosa – 1 in 1000 white women
8 Ovarian causes
Hypogonadotrophic hypogonadism -failure of the ovary to secrete sufficient oestrogen to produce endometrial growth if the follicles are damaged as a result of infection, interference with blood supply or depletion caused by bilateral cystectomies
Premature ovarian failure – hypoparathyroidism, Hashimoto’s thyroiditis, ovarian irradiation, Addison’s disease
No evidence of autoimmune disease – antibodies to gonadotrophins as well as to thyroid and adrenal glands, e.g. non-organ-specific antibodies, mainly antinuclear antibodies or rheumatoid factor

It has a 1-2 per cent complication rate, including injury to bowel or blood vessels, postoperative infection and a mortality rate of 8 in 100000.

Male partner

It is rare that any drugs can be given to improve sperm count. Therefore, use has to be made of what sperm are present. Normal sperm parameters are identified by defined criteria. Semen characteristics can be further defined as to degrees of asthenozoospermia and oligozoospermia and types of morphology. Treatment is in the form of

  • ■  Intrauterine insemination
  • ■  In vitro fertilisation
  • ■  Intracytoplasmic sperm injection.

Obstructive azoospermia is not a common cause of infertility. Obstructive azoospermia and primary spermatogenic failure account for only about 2 per cent of infertility. The exception is vasectomy reversal where success rates range from 17 to 82 per cent, depending on the length of time since the operation and any other complicating factors.

Treatment of Male Infertility

Ovulation Disorders And Ovulation Induction

In Vitro Fertilisation

Tubal  Surgery

  • ■  Tubal surgery has not been made redundant by In vitro fertilisation. If the tubes are thin walled, with little muscle fibrosis and reasonable mucosa, over one third of women will achieve a live birth subsequently, and half of those will go on to have a second live birth.
  • ■  Microsurgery enables avoidance of damage to delicate serosal and coelomic surfaces.
  • ■  Magnification (by loupes (x10) or microscope – focal length 200-300 mm) is necessary for tubal surgery in dealing with a tubal diameter of 0.5 mm.
  • ■  The main indication for tubal surgery is tubal block caused by pelvic inflammatory disease, endometriosis (at the cornual end) or congenital anomalies.
  • ■  Salpingostomy is the opening of a totally blocked fimbrial end.
  • ■  Fimbrioplasty is used for fimbrial phimosis or when there is a fibrous ring partly obstructing the fimbrial end.
  • ■  Salpingolysis is the division of adhesions around the tube.
  • ■  Salpingotomy – incision in the tube wall and inspection of the lumen – is usually associated with ectopic pregnancy.
  • ■  Diathermy dissection gives clean results and can largely be bloodless. Cutting diathermy is by a fine needle of 4-5W (monopolar).

Instruments

  • ■  Microsurgical instruments should be used, with needleholders to hold a suture of 140 µm in diameter (up to 8/0 non-absorbable nylon). Polypropylene amide (prolene) is also ideal because of its lack of tissue reaction.
  • ■  Fine probes made of Teflon or glass are useful for handling tissues and supporting them during dissection. They reduce abrasion or trauma that would be caused by handling with gloved fingers.
  • ■  The steridrape used has a 15 cm ring which can be inserted inside the wound at the start of laparotomy. It prevents leakage of blood into the abdominal cavity, reducing the risk of serious peritoneal abdominal wall adhesions after surgery.

The prognostic variables for reversal of sterilisation are maternal age and tubal length of >4cm with intrauterine pregnancy.


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