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Infertility


Infertility
Definition and aetiology
Infertility is defined as the inability to conceive after 1 year of unprotected intercourse. It is estimated that the chances of a couple conceiving are 85% after 1 year and 95% after 2 years (in women under the age of 35). Infertility is primary (no previous pregnancies) or secondary (previous pregnancy, regardless of outcome). A number of factors lead to difficulty in conceiving (Figure 30.1):

Age The prevalence of infertility rises significantly with advancing female age. Fertility rates fall moderately between age 35 and 39, and dramatically thereafter.
Anovulation This accounts for 20% of cases and is usually indicated by menstrual dysfunction: amenorrhoea, oligomenorrhoea or polymenorrhoea.
Tubal factors Pelvic infections (pelvic inflammatory disease; PID), most commonly caused by Chlamydia trachomatis, result in damage to the fallopian tubes in a significant number of women, and are often clinically ‘silent’.
Cervical mucus factors.
Male factors.


Evaluation of the infertile couple
History
Both the male and female partner needs to be evaluated. In some cases, such as amenorrhoea, azoospermia or bilateral tubal obstruction, the aetiology is obvious but in most couples the cause is less clear. The history should enquire about any previous pregnancies, previous gynaecological history, menstrual characteristics, sexually transmitted infections, medical illnesses, family history and drug history. In men, a history of previous testicular surgery, trauma or orchitis should be sought. Couples should also be questioned about the frequency and timing of sexual intercourse, and any symptoms of sexual dysfunction such as loss of libido, erectile dysfunction or dyspareunia (painful intercourse).

Examination
A general examination should include measurement of BMI, as women who have a normal BMI are more likely to conceive than those who are either under or overweight. Signs of androgen excess (acne, hirsutism) suggests a diagnosis of PCOS (Chapter 26) while a pelvic examination can reveal nodules, tenderness or limited pelvic organ mobility in keeping with endometriosis. BMI should also be assessed in men, in addition to a search for features of hypogonadism (Chapter 28).

Investigations
General health screening should include measurement of blood pressure, BMI, urinalysis, cervical cytology and rubella immunity (Table 30.1). Other tests include the following:
·   Ovulation function Regular menstrual cycles are a sign of ovulation in 95% of cycles. A midluteal phase (day 21) progesterone level can help confirm the presence of ovulation. If periods are irregular then measurement of other hormones is necessary (prolactin, thyroid function, androgens; Chapter 25). Measurement of anti-Müllerian hormone levels can help predict ovarian reserve.
·      Tubal assessment Needed when ovulation status and semen analysis is normal, especially in women with a history of PID. Laparoscopy is the gold standard.
· Uterine evaluation Transvaginal ultrasound helps assess uter-ine morphology and neighbouring structures.
·      Chlamydia serology The best initial screen for tubal disease.
·  Semen analysis Semen volume, sperm count, motility and morphology are assessed. Testosterone, FSH, LH and prolactin should be measured in men with oligospermia or azoospermia (absent sperm). Urological assessment is needed in azoospermic men with normal testosterone, LH and FSH as this indicates mechanical obstruction.

Management
·    Tubal and uterine disease Surgery can be considered for proximal tubal disease or uterine fibroids in selected patients.
·   Endometriosis Laparoscopic ablation or resection of endometriotic deposits plus adhesiolysis may be beneficial.
·    Ovulatory dysfunction Optimisation of BMI helps restore ovulatory cycles in women who are under or overweight. Ovulation induction with pulsatile GnRH analogues or gonadotrophins can be offered to patients with hypogonadotrophic hypogonadism. Antioestrogens such as clomifene citrate are used first line to induce ovulation in women with PCOS whereas patients with hyperprolactinaemia are treated with dopamine agonists (Chapter 6).
·       Intra-uterine insemination Involves timed insemination of sperm into the uterus. Often undertaken after failed ovulation induction in women with patent tubes.
·       In vitro fertilisation (IVF) and ICSI IVF treatment involves a series of steps that include superovulation (ovulation induction), oocyte (egg) retrieval, IVF, embryo transfer and luteal phase  support.
·   Oocyte donation Used in women with premature ovarian failure (e.g. Turner’s syndrome, oophorectomy, previous chemo-/radiotherapy).
·      Male factor infertility Gonadotrophins or pulsatile GnRH ana-logue therapy can improve fertility in men with hypogonado-trophic hypogonadism (e.g. Kallmann’s syndrome; Chapter 28). Hyperprolactinaemia is treated with dopamine agonists. Surgery or percutaneous sperm aspiration can improve fertility in men with obstructive azoospermia.