05 Nov Fertility | specific causes
Where the risk of damaged tubes is very high such as previous ectopic pregnancy, pelvic infection or severe endometriosis, going straight to laparoscopy is warranted.
Fertility treatment depends on the extent of tubal damage and female age. In women younger than 35 years, an attempt at laparoscopic tubal repair may be made. However, the success of this approach is only about 30%. Optimally, in vitro fertilisation (IVF) will give better fertility prospects over a shorter duration of time. If the fallopian tubes are damaged and have trapped fluid (hydrosalpinx), it is best to remove the damaged tube prior to embarking on IVF. This way, success rate with IVF is enhanced. Women with tubal damage have a higher risk of establishing an ectopic pregnancy and should have an earlier ultrasound scan to determine location of pregnancy sooner after a positive pregnancy test whether conception is natural or through IVF.
Regular menstrual cycles are an important indicator of ovulation. Cycle length between 24 – 32 days are normal whereas shorter or longer cycles are likely to go without ovulation. Most women with ovulatory problems (8 in 10) will have polycystic ovary syndrome (PCOS). Polycystic ovary syndrome is a collective term that represents a metabolic and hormonal changes manifesting as lack of ovulation, increased sensitivity to testosterone and polycystic ovaries as seen on ultrasound scan. Any two out of these symptoms make the diagnosis of PCOS. However, before the diagnosis is made, all other causes of anovulation and excess testosterone activity must be excluded. Whereas the exact cause of PCOS is unknown, the condition is characterised by resistance to the hormone insulin essential for glucose utilisation. This resistance may result from increased fat cells which do not use glucose very efficiently, causing the pancreas to increase insulin production.
Increased insulin activity makes the ovaries produce more testosterone which in turn inhibits or slows down ovulation and drives skin hair growth and acne. Fertility treatment for PCOS involves measures that restore regular ovulation. At the first instance, a reduction of 5 percent weight makes fat cells more efficient in glucose utilisation. This lowers insulin levels with resultant normal testosterone production, leading to maturation of follicles and ovulation. There are other key benefits of normal weight including reduced risk of miscarriage, fetal abnormalities, pregnancy hypertension and diabetes mellitus. Where a pregnancy has not occurred despite normal weight, medication is recommended to aid ovulation. This approach carries nearly 50% chance of achieving a pregnancy within 6 months. There is however a risk of multiple pregnancy and this treatment needs to be monitored by a specially trained practitioner.
Women with polycystic ovary syndrome who have not conceived despite weight optimisation and ovulation induction may consider in vitro fertilisation. This is also indicated where other conditions co-exist with PCOS such as blocked fallopian tubes or severely low sperm concentration.
Other causes of anovulation
Infrequently, women may have other conditions that affect normal ovulation. Usually, these will be diagnosed after a hormone profile test. Very low body weight from extreme athletic practice or eating disorders causes decreased production of follicle stimulating (FSH) and luteinising (LH) hormones. As these hormones are essential for growth of follicles and ovulation, low levels remove this key drive.
In this situation, treatment involves ovulation induction using injectable preparations of FSH and LH once the fallopian tubes and semen parameters are established to be normal.
In about 1% of women before their fortieth birthday, there is premature depletion of ovarian follicles manifesting as irregular or no periods. This is known as premature ovarian insufficiency (POI).
Whereas about 2 in 3 women with premature ovarian insufficiency have no obvious cause there may be clear reasons for ovarian failure in the rest. These include conditions that cause accelerated follicle loss like previous chemotherapy or radiotherapy treatment and genetic or autoimmune conditions. Surgery to remove ovarian cysts for instance endometriosis or complete removal of the ovary also risks premature ovarian insufficiency. Long-term use of contraceptives is not a cause of ovarian insufficiency. Women with POI have severely compromised ovarian reserve and the prospect of achieving a pregnancy lies with oocyte donation.
Before the menopause, oestrogen hormone is produced in the ovaries. It is essential for bone health, cardiovascular and urogenital vitality. A lack of oestrogen before age of the natural menopause predisposes to a higher risk of bone fragility, cardiovascular disease and compromised sexual function. There is also reduced quality of life from hot flushes, sleep disturbance and mood instability. It is therefore essential that women are put on hormone replacement therapy when premature ovarian insufficiency is diagnosed until the age of natural menopause.
Male Factor subfertility
Often male factor subfertility is only discovered after a formal sperm analysis, even though nearly 50% of cases of subfertility result from male related factors. Diagnosing male subfertility requires a thorough medical history and examination complemented by assessment of a semen sample. Delayed puberty, testicular surgery or cancer treatment may be important pointers to an existing male fertility problem. A key step in diagnosing male subfertility requires examination of a semen sample in the laboratory. This is produced following 2 to 5 days of abstinence.
Normal parameters include sperm concentration above 15 million per millilitre of semen and progressive motility above 32 percent. Where these parameters are low, repeating the examination after about three months is recommended as fluctuations are very common and there could have been problems with the initial sample collection including spillage.
Reassuringly, mild decline in sperm concentration (5 million per millilitre and above) can achieve conception when no female factors co-exist. Where sperm concentration is below 5 million/ ml, realistic chances for a pregnancy lie with assisted reproductive treatment with intra-cytoplasmic sperm injection (ICSI). This involves stimulating the female partner to produce multiple oocytes which are then retrieved and injected with sperm in a specialised treatment centre.
There are instances where no sperm is found on the semen sample. This may be due to compromised production or blockage of testicular ducts. A distinction between these is made by performing further tests.
These tests include hormone profile (follicle stimulating hormone and testosterone) and scrotal ultrasound. A specialist in fertility treatment will be to hand to help in interpreting the tests and offer appropriate treatment options. Referral to a urologist is necessary where an abnormal testicular mass is detected to exclude a malignancy. .
There is still a good chance for a biological child even in men with no sperm on the ejaculate (azoospermia). In this situation, surgical retrieval of sperm from the testes, freezing the sperm and performing ICSI treatment achieves pregnancy rates similar to couples undergoing in vitro fertilisation for other reasons.
It is not necessary to undergo testicular biopsy without the option of freezing sperm as this presents a lost opportunity when sperm is found.
Whereas lifestyle factors such as extremes of weight and smoking may affect sperm count and would be advisable to correct, disappointingly, there are no medications to restore sperm production. The exception is in men with very low FSH levels. Inasmuch as testosterone level is decreased in testicular failure, administration of testosterone is detrimental to sperm production and would be inadvisable prior to fertility treatment. This is also the case in men using performance enhancing anabolic steroids where sperm production becomes compromised.
If your periods are irregular or they do not occur and the doctor makes a diagnosis of ovulation problems, then ovulation induction is the treatment of first choice. The commonest cause of ovulatory problems is polycystic ovary syndrome. There is no added benefit in taking medication for ovulation induction if your periods are regular because ovulation is already occuring. Various medications are available for ovulation induction including letrozole, clomiphene citrate, gonadotropins and tamoxifen. For several decades, clomiphene citrate (clomid®) was used for ovulation induction. Whereas most women ovulated with clomid® use, only about half achieved a pregnancy. There are also concerns about prolonged use of clomid®. Due to these reasons, the first line medication has since been updated.
Letrozole is now recommended for ovulation induction in women with polycystic ovary syndrome. It achieves reasonable pregnancy rates up to 50% by six cycles of treatment. There is no added advantage in taking the medication for longer than six cycles. Whereas injectable gonadotropins achieve similar pregnancy rates, it is not cost-effective to have this option. Ovulation induction using injectable gonadotropins is recommended for women with reduced production of the hormone FSH and LH. This treatment requires intensive monitoring of follicle growth using ultrasound scanning in addition to ovulation triggering.
Laparoscopic ovarian diathermy (drilling) was indicated where there was clomid® resistance. This is not the case with letrozole and should therefore not be routinely offered.
Intrauterine insemination involves the placement of prepared sperm into the uterus at the time ofovulation. It may be done in a timed natural cycle or following ovulation induction. It is only helpful to have intrauterine insemination where regular intercourse is not feasible or inadvisable. Intrauterine insemination benefits a couple who are separated by a large physical distance, discordance for viral infection, single or when using donor sperm where the male partner has azoospermia (no sperm on semen analysis).
Severely low sperm count is not suitable for intrauterine insemination as the success rate is extremely very low. In this situation, in vitro fertilisation and intracytoplasmic sperm injection is advisable.
In vitro Fertilisation (IVF)
There is now ample evidence that in vitro fertilisation is an effective and safe option for fertility treatment, being in existence for 40 years. In vitro fertilisation is indicated when there is tubal blockage, severely low sperm count, azoospermia (with use of surgically retrieved sperm or donor sperm) or when there is a combination of male and female factors. If intermediate options for fertility treatment are unsuccessful, IVF offers a better chance of
conceiving a pregnancy as this is more cost-effective. This includes couples with unexplained subfertility who have tried to conceive longer than 2 years.
In vitro fertilisation involves stimulating the ovaries using injectable gonadotrophins (FSH) to achieve multiple follicle growth. When the follicles attain a specific size, oocytes are retrieved and fertilised in the laboratory. Women are given sedation for oocyte retrieval. The embryos created are grown in the laboratory for a few days when selection of the strongest embryo is done and placed in the womb. The embryo is supported to implant by using progesterone until a pregnancy is established and confirmed on ultrasound scan.
Spare embryos of good quality are then kept in storage for future use.
Whereas IVF is effective in achieving a pregnancy, it carries unique risks which require to be minimised. Multiple pregnancy is the commonest risk following IVF treatment due to placement of multiple embryos in the womb. This has several risks for both the mother and fetuses which are largely prevented by replacement of a single embryo. A robust cryopreservation (freezing) programme helps to achieve this endeavour and requires a responsible practitioner to appropriately counsel the patients.
Whereas the goal in IVF is to achieve multiple oocytes to optimise the odds of good quality embryos, a few women unfortunately may be too sensitive to the medication recruiting too many follicles. This may result in a condition known as ovarian hyperstimulation syndrome (OHSS). This is unpredictable, however, women with a high ovarian reserve (anti-Mullerian hormone [AMH]), young (<35 years), low BMI or previous OHSS are at a particularly increased risk. The antagonist protocol significantly reduces the risk of OHSS during IVF.