Infertility

Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child

Aetiology

Definitions

• Either primary (couple never conceived) or secondary (couple previously conceived, although pregnancy may not have been successful e.g. miscarriage, ectopic pregnancy)

• Infertility is classed as a disease as it causes considerable psychological distress

Factors which increase chance of conception

• Women under 30

• Previous pregnancy

• Less than 3 years trying to conceive

• Intercourse occuring around ovulation

• Woman's BMI 18.5-30 m/kg2

• Both partners non-smokers

• Caffeine intake of less than 2 cups a day

• No recreational drug use

Causes of female infertility

• Infertility due to lack of ovulation

• Physiological
• Before puberty, pregnancy, lactation, menopause

• Gynaecological conditions
• Hypothalamic: anorexia/bulimia, excessive exercise, stress, Kallman's syndrome
• Pituitary: hyperprolactinaemia, tumours, Sheehan syndrome
• Ovarian: PCOS, premature ovarian failure

• Others
• Systemic disorder e.g. chronic renal failure
• Endocrine disorder e.g. testosterone secreting tumours, congenital adrenal hyperplasia, thyroid
• Drugs e.g. depo-provera, explanon, OCP

• Tubal disease

• Fibroids

• Endometriosis/adenomyosis

• Weight related

• Age related

Causes of male infertility

• Approx. 30-50% idiopathic

• Environmental and lifestyle factors are risk factors e.g. occupational, smoking, alcohol, obesity

• e.g. 47 XXY (Klinefelter), chemotherapy, radiotherapy, undescended testes, idiopathic, endocrine causes (hypogonadotrophic hypogonadism, hypothyroidism, hyperprolactinaemia, diabetes)

• Clinical features:
• Low testicular volume
• Reduced secondary sexual characteristics
• Vas deferens present

• Endocrine features: high LH and FSH, low testosterone

• e.g. congenital absence (CF), infection, vasectomy

• Clinical features:
• Normal testicular volume
• Normal secondary sexual characteristics
• Vas deferens may be absent

• Endocrine features: normal LH, FSH and testosterone

Clinical presentation

History taking (male and female)

• Infertility history

• Gynaecology

• Andrology

• PMHx, PSHx, POHx - ask about menstrual cycle for female

• Sexual history

• Social history

Examination - female

• BMI

• General examination, assessing body hair distribution, galactorrhoea

• Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility

Examination - male

• BMI

• General examination

• Genital examination, assessing size/position testes, penile abnormalities, presence of vas deferens, presence of varicoceles

Investigations

Primary care investigations

• Assessing ovulation
• Regular cycles very suggestive of ovulation
• Confirm with midluteal progesterone level - day 21 of 28 day cycle or 7 days prior to expected period in prolonged cycles
• Irregular cycles - likely anovulatory, needs further hormone evaluation

• Blood for rubella immunity
• Checking for rubella IgG (immunity) is important as if mother contracts rubella while pregnant there is a 50% chance baby will get rubella syndrome - effects include microcephaly, patent ductus arteriosus, cateracts
• Can be avoided by giving MMR booster

• TSH

• Endocervical swab for chlamydia
• If a woman has one untreated chlamydia infection, the chances of tubal block is 10%

• Cervical smear if due

• If amenorrhoeic/cycle longer than 42 days:
• Follicular phase bloods: LH, FSH, E2
• Testosterone, SHBG, FAI
• Prolactin

• Diagnostic semen analysis - twice over 6 weeks apart
• Azoopermia: no sperm in ejaculate
• Asthenozoospermia: % progressive motile sperm below reference limit
• Oligozoospermia: total number/concentration of sperm below reference limit
• Teratozoospermia: % morphologically normal sperm below reference limit

Infertility consultation

• Patients seen as a couple

• Establish length of relationship, and length of time trying to get pregnant

• Ultrasound - abnormal findings include congenital uterine abnormalities, fibroids, endometrial polyp, hydrosalpinx, PCOS, ovarian cyst

• Tubal patency testing
• Hysterosalpingiogram (HSG)/hycosy - if no known risk factors for tubal or pelvic pathology, or if laproscopy contraindicated
• Diagnostic laproscopy - if possible tubal/pelvic disease, known previous pathology, history suggestive of pathology or previously abnormal HSG
• Contraindicated in obesity, previous pelvic surgery, Crohn's disease

• Hysteroscopy - only performed in cases where there is suspected/known endometrial pathology

• If abnormal semen analysis: LH and FSH, testosterone, prolactin, thyroid function

• If severely abnormal semen analysis/azoospermic:
• Endocrine profile as in abnormal semen
• Chromosome analysis and Y chromosome microdeletions
• Screen for cystic fibrosis
• Testicular biopsy

• If abnormality on genital examination:
• Scrotal US

Management

Lifestyle advice

• Stop smoking

• Achieve BMI between 18.5 and 30

• Reduce/stop alcohol intake

• Take caffeine containing drinks in moderation only

• Stop recreational drugs

• Stop taking methodone

General advice

• Reassurance - 95% will conceive within 36 months of unprotected sex

• Advise sexual intercourse every 2-3 days rather than timing intercourse with the menstrual cycle

• Consider underlying psychosexual problems

• Consider need for preconception counselling if pre-existing medical condition e.g. euglycaemic control if women diabetic

Management of female infertility

• Folic acid - 400 micrograms daily before pregnancy and for first 12 weeks (5 milligrams in some cases e.g. woman or or their partner have a damily history of neural tube defects)

• Vitamin D - 10 micrograms per day for pregnant or lactating women

• Stabilise weight - BMI >18.5 and <30

• Lifestyle modification - smoking, alcohol

• Folic acid 400 mcg daily, 5mg daily if BMI over 30

• Check prescribed drugs

• Check rubella immunity

• Normal semen analysis

• Patent fallopian tube

• Treat any cause of fertility issues e.g. ovulation disorders
• PCOS is the most common reason for ovulatory problems → ovulation induction
• Clomifene citrate/letrozole first line for ovulation induction, gonadotrophin injections and laproscopic ovarian diathermy are other options
• If clomifene resistant: weight loss, consider adjuvant metformin

• Reproductive surgery may be the primary treatment of infertility e.g. devision of pelvic adhesions, removal of tubal block and removal of polyps/fibroids

• Surgery can also be used to enhance IVF treatment
• Women with hydrosalpinges (fallopian tube filled with water) should be offered laparoscopic salpingectomy before IVF treatment as this improves pregnancy rate and reduces miscarriage rate
• Abnormalities in the uterine cavity should be treated before IVF

Management of male infertility

• There are only a few treatable causes e.g. prescribed drugs, surgery to obstructed vas deferens, hormonal conditions

• Treatment mainly rests with ART
• Intrauterine insemitation in mild disease
• Intracytopalsmic sperm injection (ICSI) - microinjection of the sperm into the egg
• Surgical sperm aspiration (surgical sperm recovery) from epididymis or testicle combined with ICSI
• Donor sperm insemination if no sperm found in aspiration

Assisted conception

1. Pre IVF workup

2. Ovarian stimulation (hormonal injection)

3. Monitoring

4. Ovulation induction

5. Oocyte removal

6. Preparation of sperms

7. In vitro ferilization

8. Embryo transfer - once embryo reaches the blastocyst stage (day 5)

9. Luteal support

• Ovarian hyperstimulation
• Usually occurs in women taking injectable hormone medication e.g. ovulation induction, IVF
• Affects up to 10% of IVF cycles
• Ranges from mild-severe
• Increased risk if <35 years, PCOS

• Multiple pregancy
• Increased maternal and pregnancy complications, as well as risk for babies

• Theoretical risk of ovarian cancer