Definition of infertility
Infertility is the failure to conceive after having regular unprotected sexual intercourse (every 2-3 days) for one or two years (approximately 50% of women who do not conceive in the first year are likely to do so in the second year.)
What proportion of couple will concieve naturally within 1 year and after 2 years of intercourse. What are the chances after 3 years
- 84% of couples in the general population will conceive naturally within 1 year with regular unprotected intercourse, rising to 92% after 2 years and 93% after 3 years
- For couples who have been trying to conceive for more than 3 years, the chance of a spontaneous pregnancy in the next year is 25% or less
How can infertility be calssified
- Primary in couples who have never conceived
- Secondary in couples who have previously conceived
How is subfertility defined
Generally describes any form of reduced fertility that results delayed conception
What is the incidence of subfertility
- 1 in 7 couples have difficulty conceiving and female fertility declines with age- most important factor affecting fertility (affect of paternal age is unclear)
- Female fertility falls sharply at the age of 36
What is the process (timeline) of natural conception
- Eggs are fertilisable for about 12-24 hours after ovulation
- Sperm can survive within the female reproductive tract for up to 72 hours
- Ovulation usually occurs 14 days before menstruation
- The fertile window will be different depending on the usual length of the cycle
ALL WOMEN who intend to concieve should commence folic acid (400mcg/day)
What are some lifestye factors which confer risk of infertility
smoking, extremes of BMI, excess exercise and stress
What are the main causes of infertility
Ovulatory disorders (25% of couples), tubal damage (20% of couples), male infertility (30% of couples) and uterine and peritoneal disorders (10% of couples). Gamete or embryo defects, uterine or endometrial factors, and pelvic conditions such as endometriosis may also have significance.
* Thee is no identifiable cause of infertility in 25% of couples
What are some male causes of infertility
- There many be no underlying cause (44% of cases), however semen analysis might reveal decreased number of spermatozoa (oligozoospermia), decreased sperm motility (asthenozoospermia), abnormal sperm on morphological examination (teratozoospermia)
- Identifiable causes include primary spermatogenic disorders- genetic disorders, obstructive azoospermia, varicocele, hypogonadism, vasectomy, stress, lifestyle factors
Can also be divided into pre-testicular, testicular and post-testicular factors of male infertility
What are some cuases of primary spermatogenic failure (any spermatogenic abnormality caused by a condition other than hypothalamic disease)
- Congenital- Anorchia (absence of testes), testicular dysgenesis/ cryptorchidism (undescended testes), genetic abnormalities (karyotype, Y-chromosome deletion), Obstructive azoospermia (absence of both spermatozoa and spermatogenic cells in semen and post-ejaculate urine due to bilateral obstruction of the seminal ducts- can be congenital or acquired)
- Acquired- Trauma, testicular torsion, mumps orchitis, exogenous factors (medication cytotoxic or anabolic drugs, irradiation, heat), systemic disease, testicular tumour, varicocele, ejaculation disorders or erectile dysfunciton
What are some genetic causes of male infertility
Klinefelter’s syndrome with karyotype 47 XXY, Kallmann syndrome, small testes, cystic fibrosis, androgen insensitivity syndrome
What is the management of male factor infertility
- Lifestyle modification (particularly where there is teratozoospermia)- stop smoking, reduce alcohol intake and lose weight
- Men with hypogonadotropic hypogonadism should be offered gonadotrophin drugs since they are effective in improving fertility
- Men with idiopathic semen abnormalities should not be offered anti-oestrogens, gonadotrophins, androgens, bromocriptine or kinin-enhancing drugs because they have not been shown to be effective. Effect of corticosteroids has also been shown to be unclear.
- Men with obstructive azoospermia should be offer surgical correction of epididymal blockage
- Men should not be offered surgery for varicoceles as part of fertility treatment (does not improve pregnancy rates)
- Intrauterine insemination or intracytoplasmic sperm injection (direct injection of sperm into the cytoplasm of an egg)
Describe the normal physiology of ovulation
- Low oestrogen-> positive feedback on the hypothalamus and results in GnRH pulsatility
- This leads to release of FSH and LH
- FSH causes growth and maturation of several follicles in the ovary, each of which contains an immature oocyte
- Follicles produce oestradiol which has a negative feedback effect on the hypothalamus and causes suppression of FSH and LH
- The dominant follicle has sufficient gonadotrophin receptors to survive, it produces inhibin B which further suppresses FSH
- High oestradiol output eventually causes an LH surge, once a threshold potential has been reached
- Casues rupture of the follicle. The egg is collected by fallopian tube fimbrae and the follicle becomes a corpus luteum-> progesterone production-> secretory endometrium.
How can anovulation be classified (THREE classifications)
- Group 1 ovulation disorders (hypogonadotropic hypogonadism) are caused by hypothalamic pituitary failure. This includes conditions such as hypothalamic amenorrhoea (commonly due to low body weight or excessive exercise), Sheehan’s, Kallmann’s syndrome. Accounts for around 10% of women with anovulation. Women typically present with amenorrhea, characterised by low gonadotrophins and oestrogen deficiency.
- Group II ovulation disorders are defined as dysfunctions of the hypothalamic-pituitary ovarian axis. This includes PCOS and hyperprolactinaemic amenorrhoea (85% of women with ovulation disorders have a group II anovulation disorder)
- Group III ovulation disorders are caused by ovarian failure and are characterised by high gonadotrophins and hypogonadism and a low oestrogen level. 4-5% of women with ovulation disorders have a group III disorder.
Management of group 1 anovulation disorders
Advise women with group I disorders that they can improve their chances of regular ovulation, conception and uncomplicate pregnancy by:
* Increasing their body weight if they have a BMI of less than 19
* Moderating their exercise levels if they undertake high levels of exercise
Offer women with group 1 ovulation disorders pulsatile administration of GnRH or gonadotrophins with LH activity to induce ovulation
Management of group 2 anovulation disorders
Advise women with group 2 disorders who have a BMI of 30 or over to lose weight (this alone might restore fertility).
Offer one of the following treatments: clomiphene or metformin (when insulin insensitivity and obesity associated) or a combination of the above
* Clomiphene citrate is a selective oestrogen receptor modulator- stops negative feedback of oestrogen on the hypothalamus, increasing GnRH pulsatility
* Before starting clomiphene, give woman a progesterone fisrst to induce a withdrawal bleed so that you are at the start of the cycle
* Usually continued for 6 cycles
* For women taking clomiphene citrate, offer USS monitoring during at least the first cycle of treatment to ensure that they are taking doses that minimises the risk of multiple pregnancy and do not continue for longer 6 months
* Side effects of metformin include nausea, vomiting, GI disturbance
In women with PCOS who are resistant to clomiphene treatment can alternatively consider:
* Combination therapy (metformin + clomiphene)
* Letrozole (aromatase inhibitor with anti-oestrogen effects)
* GnRH OR GnRH agonist (not both concomitantly since risk of ovarian hyperstiulation)
* Ovarian drilling
Hyperprolactinaemic amenorrhoea- offer treatment with dopamine agonists such as cabergoline
What are some medications that can affect fertility
NSAIDs (inhibit ovulation), COX inhibitors, spironolactone (cause infertility and menstrual irregularities), chemotherapy, neuroleptics, contraceptives (especially PROVERA depot), recreational drug use
What are some tubal, uterine and cervical risk factors for infertility
STIs or PID, previous sterilisation, endometriosis (tubal distortion and limitation of fimbrial motility due to pelvic adhesions), cervical mucus defect, submucosal fibroids (may distort the uterine cavity and impair implantation), previous cervical or pelvic surgery
What surgical options exist for treating tubal/uterine causes of infertility
- Tubal microsurgery and laparoscopic tubal surgery- for mild tubal disease
- Tubal catheterisation or cannulation- May be used in women with proximal tubal obstruction- selective salpingography plus tubal catheterisation or hysteroscopic tubal cannulation
- Women with amenorrhoea who are found to have intrauterine adhesions should be offered hysteroscopic adhesiolysis
- After identification of fibroids can offer myomectomy- hysteroscopy, laparocopy, laparotomy or fibroid embolisation
- IVF
In whom is intrauterine insemination a viable treatment option
Mild endometriosis, mild male factor infertility, couples who do not have intercourse, single women, same sex couples using donor sperm, unexplained infertility
Describe the process of intrauterine insemination
- A catheter is passed through the cervix so is in the lower part of the uterine cavity. Sperm is then injected into the uterine body to allow them to pass into the fallopian tube (sperm selected are motile and morphologically normal- then concentrated)
- Sperm are usually injected 24 hours before ovulation occurs
- May be preceded by mild stimulation with SC injections of FSH (stimulates ovaries to produce 2-3 mature follicles)
- Triggering ovulation and timing the insemination may be achieved by a SC hCG injection
Investigations for male factor infertility
Semen analysis:
* Reference ranges: Semen volume (1.5ml or more), pH (7.2 or more), Sperm concentration (15 million spermatozoa per ml or more), total (39 million spermatozoa per ejaculate or more), total motility (40%) viability (58% live), morphology (4% or more normal morphology)
* If the results of the first semen analysis is abnormal a repeat confirmatory test should be offered (should be repeated after 3 months to allow cycle of spermatozoa)
* Factors affecting semen analysis: hot baths tight underwear, smoking, alcohol, raised BMI, caffeine
* Men should abstain from ejaculation for at least 3 days and at most 7 days prior to semen analysis testing, avoid hot baths, tight underwear etc.
Vasography and testicular biopsy if indicated
Investigations for female infertility
Initial investigations in women, often performed in primary care:
* BMI (low could indicate anovulation, high may subfertility, PCOS), chlamydia screening , rubella immunity in the mother
* Hormone testing: Serum LH and FSH on day 2 to 5 of the cycle
* High LH may suggest PCOS
* Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not on a 28-day cycle) if they have irregular cycles
* A rise in progesterone on day 21 indicates that ovulation has occurred and that the corpus luteum has formed
* AMH
* TFTs where symptoms are suggestive
* Prolactin (if hyperprolactinaemic anovulation is suspected)- galactorrhoea or amenorrhoea
Ovarian reserve testing:
* A woman’s age should be used as an initial predictor of chances of success in natural conception or IVF
* One of the following then can be used to predict the likely response to GnRH stimulation in IVF: Total antral follicle count- Greater than 16 indicates high reserve, less than 4 indicates low reserve and likelihood of IVF success, AMH- can be measured at any time in the menstrual cycle (greater than 25 indicates high reserve, less than 5.5 indicates low reserve)-> Produced by granulosa cells and does not change in response to gonadotrophins, so it is the most successful biomarker of ovarian reserve
* FSH- greater than 8.9 IU/l for a low reserve, and less than 4 IU/l for a high reserve
Pelvic USS- to look for PCOS or structural abnormalities of the uterus
* Also allows for assessment of antral follicle count
Hysterosalpingogram- to look at the patency of fallopian tubes
* Usually only performed when there are risk factors for tubal damage (previou
* A type of scan used to assess the shape of the uterus and patency of the fallopian tubes- also of therapeutic benefit since tubal cannulation under x-ray guidance can be performed during the procedure to open up the tubes
* A small tube is inserted into the cervix, a contrast medium is injected through the tube and fills the uterine cavity and fallopian tubes. X-ray images are then taken (shows abnormalities + obstruction
* There is a risk of infection, so prophylactic antibiotics are given and screening for chlamydia and gonorrhoea are completed before the procedures ectopic, endometriosis PID)
Laparoscopy and dye test- to look at the patency of fallopian tubes, adhesions and endometriosis
* Same idea, but during laparoscopy
People undergoing IVF treatment should be offered testing for HIV, hepatitis B and hepatitis C
What intial advice should be given for infertility
- People who are concerned about their fertility should be informed that over 80% of couples in the genera population will conceive within 1 year if:
- The woman is aged under 40 years and they do not use contraception and have regular sexual intercourse (of those wo done not half will do so within the second year)
- Over 50% of women aged under 40 years will conceive within 6 cycles of intrauterine insemination (IUI) (half of those remaining will do some with a further 6 cycles)
- Women who are trying to become pregnant should drink no more than 1 to 2 units of alcohol once or twice per week (3 to 4 units per day for men)
- Women who smoke should be informed that this is likely to reduce their fertility (same for men)
- Women with a BMI > 30 should be informed that they are likely to take longer to conceive and that losing weight will increase their chances of conception
- Women who have a BMI < 19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight will improve their chance of conception
- Men should avoid wearing tight underwear
- Dietary supplementation with folic acid before conception and up to 12 weeks’ gestation reduces the risk of having a baby with neural tube defects (should take 0.4mg per day)
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Menopause36
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PCOS16
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Subfertility34
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Bacterial Vaginosis and Vulvovaginal Candidiasis24
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Pelvic Inflammatory Disease and Endometritis23
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Endometriosis15
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Female Genital Mutilation12
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Lichen Simplex, Planus and Sclerosis19
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Ovarian Cysts17
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Premenstrual syndrome13
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Pruritis Vulvae10
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Fibroids and Menorrhagia22
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Benign Lesions29
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Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer39
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Endometrial Cancer and Endometrial Hyperplasia22
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Ovarian Cancer18
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Vulvar cancer20
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Urinary Incontinence36
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Urogenital Prolapse17
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Ectopic Pregnancy19
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Gestational Trophoblastic Disease16
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Hyperemesis Gravidarum9
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Miscarriage13
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Termination of Pregnancy10
