Gab Kovacs1 and Paula Briggs2
(1)
Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
(2)
Sexual and Reproductive Health, Southport and Ormskirk Hospital, Southport, UK
Definition
Incidence
Aetilogy and Pathogenesis
Clinical Assessment
History
Examination
Investigations
Treatment (Fig. Flow Chart)
Medical
Surgical
Complications
Prognosis
IVF
Definition
Failure to conceive after 12 months of unprotected sexual intercourse
Incidence
It is said that 15 % of couples have subfertility. This seems to be true for most of the world, unless there are pockets of problems peculiar for a particular population, where the incidence rates can be higher.
Aetilogy and Pathogenesis
Subfertility can be divided into the following potential causative factors (Fig. 16.1):
Fig 16.1
Three basic fertility parameters
· SPERM- The right “number” of sperm have to be deposited, in the right place, at the correct time.
· OVULATION- The woman has to release an egg
· TUBES- The passages, cervix, uterine cavity and tubes have to be patent
· MIXED – more than one factor
· UNEXPLAINED (IDIOPATHIC) SUBFERTILITY
· Transport problem
· Fertilisation problem
· Implantation problem
Clinical Assessment
History
If possible a couple should be seen together
· Previous fertility history- both partners
· Menstrual history
· Medical History, including cervical smear history
· Surgical History
· Medications including alcohol, recreational drugs, and smoking
· Family History, especially congenital abnormalities, endometriosis
· Social History-
· Sexual History- Intercourse timing and adequacy
Examination
Routine abdominal, speculum and vaginal examination. Opportunistic cervical smear if indicated
Investigations
Female
· Infection screens- Rubella and ?Varicella Immunity (dependent on country)
· Hormones: Mid luteal progesterone and oestradiol
If cycles irregular: FSH, LH, Prolactin, TSH
Male
· Semen analysis on a specimen produced by masturbation
· Antisperm antibodies
· A semen analysis should always be performed before undertaking tubal assessment of the female. If normal, consider tubal assessment
· Hysterosalpingogram (HSG)- (Fig. 16.2) An X-ray contrast test- cheap, widely available, painful, false positives and negatives, limited information.
Fig 16.2
Hysterosalpingigram
· HyCoSy (Ultrasound with positive contrast) – (Fig. 16.3) an ultrasonic investigation- more expensive, less available, less uncomfortable, gives information on uterus and ovaries, won’t diagnose endometriosis, will not assess the status of tubes any more than patent/blocked. False positives due to tubal spasm.
Fig 16.3
HyCoSy
· Laparoscopy with dye studies (Fig. 16.4) – Most expensive, most invasive (GA, day surgery), “gold standard”- visualisation of tubes, ovaries and uterus. Provides potential diagnosis and opportunity to treat underlying disease e.g. endometriosis.
Fig 16.4
Laparoscopy
If ovulation, sperm and tubes all normal- unexplained subfertility.
Possible explanation:
· Transport problem
· Fertilisation problem
· Implantation problem
Need IVF to diagnose and/or treat
Treatment (Fig. 16.5 Flow Chart)
Fig 16.5
Flow chart for investigating sub fertility
Medical
Hormonal
· Women who do not ovulate regularly should have ovulation induction
· Check Prolactin level – if elevated normalise using bromocryptine or cabergoline. If significantly elevated (>4 times normal) investigate pituitary by imaging CT scan/MRI scan. Once ovulation is restored, conception should occur
· If prolactin is normal, use clomiphene citrate. Usually administered daily from Day 5 to 9 of a cycle or after a period or hormone induced bleed.
· Commence with low dose (25 mg) and increase monthly until regular ovulation.
· Monitor with mid luteal oestrogen and progesterone, and sometimes ultrasound
· If no response to clomiphene at 150 mg/day progress to FSH injections
· Sixty to eighty percent of women ovulate with clomiphene and about 50 % conceive.
· Ovulation induction with FSH injections needs to be undertaken in specialist centers. Daily injection of FSH, titrating the dose against the response as monitored by blood oestrogen levels and/or ultrasound scanning.
· About 20–25 % pregnancy rate per cycle, but about one in four pregnancies are multiple, usually twins.
· It is infrequent that a hormone deficiency (hypo-gonadotrophic hypogonadism) is responsible for azoospermia (no sperm). This rare condition can be treated by injections of FSH over several months, and usually responds by sperm production.
Other Medical
Metformin is sometimes used to improve ovulation in anovulatory women with Polycystic Ovarian Syndrome (PCOS), but clomiphene is more effective. Metformin and Clomiphene may be used together.
Surgical
Minor
· Women with PCOS who do not respond to clomiphene, may be suitable for laparoscopic ovarian cautery, where some of cysts on the ovarian surface are punctured and burnt. For reasons we do not understand this restores ovulation in about 50 % of women.
· Tubal surgery – If laparoscopy reveals a pelvic abnormality such as peri-tubal adhesions or endometriosis, then laparoscopic surgery can be carried out.
· In case of tubal disease, significant sperm problems, or unexplained subfertility, IVF is the treatment of choice (See Fig. 16.5 Flow Chart)
· In Vitro Fertilisation see below
Complications
Anovulation is associated with amenorrhoea and infertility
· Irregular ovulation results in oligomenorrheoa, and difficulty becoming pregnant- this can be remedied by inducing ovulation
· Anovulation will result in persistent unopposed oestrogen which acting on the endometrium, will result in hyperplasia and an increased risk of endometrial cancer.
Prognosis
Most couples can achieve a pregnancy one way or another in 2015.
· IVF can overcome most fertility problems. Women who have ovarian insufficiency can use donor eggs, men with irreversible azoospermia can sometimes have sperm extracted from their testicle used for IVF, and failing that there is the potential to use donor sperm.
· Women who have lost their uterus or are unable to carry a pregnancy for medical reasons can use a gestational surrogate.
IVF
Because IVF is a common solution for all types of subfertility, a basic outline of what it involves will be described here. IVF consists of five basic steps:
1.
2.
3.
4.
5.
6.
The chance of success for an IVF treatment cycle: The chance of pregnancy depends on the age of the woman providing the oocytes. One would expect a pregnancy rate of 40 % per cycle under 35 years, 30 % for 35–39 years, about 25 % at 40, declining to less than 5 % at 44 years of age. In the case of egg donation, the chance of pregnancy depends on the age of the oocyte donor.