Infertility: د.نادية مضر الحلي
Definition: infertility is defined as the failure to conceive within one year of unprotected regular sexual intercourse. Infertility is said to be primary if no previous conception occur while it is called secondary if previous conception occur whatever its fate.
Infertility affects about 15 % of couples. The single most important factor in determining fertility is the age of the female, fertility rapidly reducing after the age of 35 years. Other factors that reduce the chance of spontaneous conception include:
• Duration of infertility more than 3 years.
• Low coital frequency.
• No previous pregnancy.
• Smoking.
• Body mass index out side the range 20-30 kg/m2 (weight/height2) in women.
• Low number of motile healthy sperms.
Causes of infertility:
The main causes of infertility are anovulation, male factor, tubal damage & unexplained. Other causes include endometriosis & fibroids. Tubal factor is more common in patient with secondary infertility.
Ovulatory disorders:
Ovulation problems can arise as a result of a defect in the hypothalamus, pituitary or the ovary. Factors that affect the pulsatile release of GnRH will lead to disordered ovulation. These factors include stress, psychological disturbances, weight change & systemic diseases as well as tumours & structural lesions in the hypothalamus.
Hypothyroidism & hyperthyroidism may cause ovulatory failure. Hyperprolactinaemia, renal failure, hepatic dysfunction & phenothiazin drug reduce the pulsatile release of GnRH leading to anovulation.
The commonest cause of anovulatory infertility is polycystic ovary syndrome (PCOS). Women affected by this condition have a range of symptoms that include: menstrual cycle disturbance (oligomenorrhea or amenorrhea), obesity, hirsutism, acne & subfertility. The diagnosis is based on biochemical abnormality (high LH/FSH ratio & increased androgen level) & ultrasound appearance of the ovaries (enlarged ovaries with multiple small follicles & dense stroma).
Premature ovarian failure is a condition in which the ovaries fail before the age of 40 years. It is characterized by amenorrhea, raised FSH & low serum estradiol. The aetiology include genetic defect (e.g. Turner syndrome), damage due to viral infection, toxins, pelvic surgery, irradiation & cytotoxic drugs, also autoantibodies affecting the ovaries.
Tubal dysfunction:
Tubal damage may result from pelvic infection, endometriosis or pelvic surgery. This damage may cause impaired oocyte pick-up mechanisms by the fimbriae or to damaged tubal epithelium. Sexually transmitted disease caused by Chlamedia trachomatis or gonorrheaare the most common cause in addition to pelvic sepsis following appendicitis & peritonitis.
Disorders of implantation:
This include defects related to endometrial development or the production of growth & adhesion molecules. Submucous fibroid may distort endometrial cavity & impair implantation.
Male factor:
• Disorders of spermatogenesis.
• Impaired sperm transport.
• Ejaculatory dysfunction.
• Immunological & infective factors.
Management:
History & examination: A full medical & surgical history should be obtained from both male & female partner. Drug history, life style including the use of alcohol, smoking & recreational drugs. Details of coital frequency & any difficulties of coitus. Gynaecological history is important, details of menstrual cycle. If irregular menstruation, ask about symptoms of PCOS, thyroid disorders & hyperprolactinaemia.
Assessment of woman s general health, cervical smear, body weight & blood pressure.
Examination of both partners is essential to ensure normal reproductive organs.
Investigations: these should be tailored to the circumstances of individual couples. These include assessment of hypothalamo-pituitary-ovarian axis, ovulation, Fallopian tube patency & seminal fluid analysis. Early follicular phase (day 2-5 of menstrual cycle) measurement of FSH & LH to assess ovarian function. Mid-luteal progesterone level to confirm ovulation. Alternatively, serial follicle tracking by US in the midcycle can be used to confirm ovulation.
Assessment of tubal patency: tests rely on visualization of solutions passing through the tubes into the abdominal cavity. Hysterosalpingogram is performed during the follicular phase of the menstrual cycle prior to ovulation to avoid the risk of inducing ectopic pregnancy or exposing the embryo to ionizing radiation. The procedure involves instillation of a radio-opaque dye, through a small catheter placed in the cervical canal, into the uterine cavity. The x-ray image shows the uterine cavity, the outline of Fallopian tubes & the presence or absence of dye in the abdominal cavity. When the dye flows freely into the abdominal cavity it confirms patency. If the dye spill appear to be loculated or no spillage, peritubal adhesion or obstruction are likely. Uterine adhesions & submucous fibroids appear as filling defect on X-ray image & require further assessment by hysteroscopy.
Hysterocontrast sonography (HyCoSy) involves the use of US to image the uterus & fallopian tube & avoid exposure to X-ray. Normal saline is instilled into uterine cavity through a cervical catheter. It will outline the uterine cavity & delineate any filling defect. Laparoscopy & dye intubation necessitate general anaesthesia. It involves direct visualization of pelvic organs. Tubal patency is tested by installing methylene blue through thecervix & observing spillage of dye from fimbrial end.
Semen analysis: should be carried out on a sample produced after 3 days of sexual abstinence. If the analysis is not satisfactory a second sample should be analysed. The potential of sperm to fertilize is indicated by its progressive motility, morphology & agglutination. In men with very low sperm counts, an endocrine profile (LH, FSH, testosterone & prolactin is indicated. Screening for cystic fibrosis is indicated for men with azoospermia. Semen analysis includes:
• Volume: 2-5 mL
• Liquifaction time: within 30 minutes
• Sperm concentration: ? 20 million/mL
• Sperm motility: >50% progressive motility
• Sperm morphology: >30% normal forms
• White blood cells: <1million/mL
Postcoital Test: has limited prognostic value. It involves an assessment of peri-ovulatory cervical mucus & sperm in a sample obtained from the female 6-10 hours after coitus.
Treatment:
Ovulation Problems: Women with hypothalamic disorder caused by excessive weight gain or low body weight should optimize their weight & avoid stressful lifestyle. Women with hyperprolactinaemia need investigations to medical causes. If a tumour is detected, it may require surgery or shrink in response to dopaminergic agonists (e.g bromocriptin, cagergolin).
In women with PCOS, insulin sensitizing drugs eg.metformin may resume ovulatory cycles. Alternatively, ovarian drilling, in which a diathermy needle is used laparoscopically to make multiple small holes in the surface of the ovary, can be an effective treatment for anovulation linked to PCOS.
Ovulation induction can be performed using anti-oestrogen medications like clomiphene citrate & tamoxifen or gonadotrophins to stimulate the development of mature follicles. Clomiphene citrate is administered during the follicular phase of the menstrual cycle. It acts by increasing gonadotrophin release from the pituitary, leading to enhanced follicular recruitment & growth. It is effective in 85% of women & can be used for a maximum of 6-12 months to avoid the risk of ovarian cancer. Treatment should be monitored by ultrasound to avoid the risk of multiple pregnancy & ovarian hyperstimulation syndrome.
Adverse anti-oestrogenic effects of clomiphene citrate include thickening of cervical mucus & hot flushes, others include abdominal distension & pain, nausea, vomiting, breast tenderness & reversible hair loss.
Gonadotrophins are given by daily injection from the beginning of the cycle. The dose is titrated against individual response & is monitored by US assessment of the number & size of follicles. Ovulation is triggered by injection of human chorionic gonadotrophin (hCG which binds to LH receptors) when 1-3 follicles are 18 mm in diameter. If more than three follicles are present, the couples are asked to avoid aexual intercourse & hCG is withheld.
Tubal disease:
Treatment aims to restore normal anatomy. The chance of success depends on severity, location of damage & skills of the surgeon. In-vitro fertilization is an alternative to surgery. & is recommended if there is extensive damage or intrafallopian damage or if surgery failed to restore patency. Peri-tubal & periovarian adhesions can be removed by laparoscopic adhesiolysis. If fimbria are involved, fimbryoplasty to remove fimbrial adhesions can be successful. Pregnancy rate is about 50%, with 5% will have ectopic pregnancy. Reversal of sterilization produce good conception rate as the mucosal damage is limited. & the woman has proven fertility. In case of hydrosalpinges, better to remove the affected Fallopian tube prior to IVF as they affect implantation adversely.