How to Have a Baby: Overcoming Infertility
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
What is PCOD ( Polycystic Ovarian Disease) ?
How is PCOD diagnosed ?
What is the cause of PCOD ?
What is occult PCOD ?
How is PCOD treated ?
How can ovulation be induced in patients with PCOD ?
How is surgery used to treat patients with PCOD ?
How is IVF used for treating patients with PCOD ?
Patients suffering from polycystic ovarian disease (PCOD) have multiple small cysts in their ovaries (the word poly means many). These cysts occur when the regular changes of a normal menstrual cycle are disrupted. The ovary is enlarged; and produces excessive amounts of androgen and estrogenic hormones. This excess, along with the absence of ovulation, may cause infertility. Other names for PCOD are Polycystic Ovarian Syndrome (PCOS) or the Stein-Leventhal syndrome.
Polycystic Ovarian Syndrome can be easy to diagnose in some patients. The typical medical history is that of irregular menstrual cycles, which are unpredictable and can be very heavy ; and the need to take hormonal tablets (progestins) to induce a period. Patients suffering from PCOD are often obese and may have hirsutism , (excessive facial and body hair) as a result of the high androgen levels. However, remember that not all patients with PCOD will have all or any of these symptoms.
This diagnosis can be confirmed by vaginal ultrasound, which shows that both the ovaries are enlarged; the bright central stroma is increased ; and there are multiple small cysts in the ovaries. These cysts are usually arranged in the form of a necklace along the periphery of the ovary. ( It is important that your doctor be able to differentiate multicystic ovaries from polycystic ovaries. )
Blood tests are also very useful for making the diagnosis. Typically, blood levels of hormones reveal a high LH (luteinising hormone) level; and a normal FSH level (follicle stimulating hormone) (this is called a reversal of the LH : FSH ratio, which is normally 1:1); and elevated levels of androgens ( a high dehydroepiandrosterone sulphate ( DHEA-S) level) ;
Fig 1. A schematic, comparing a polycystic ovary with a normal ovary.
We don't really understand what causes PCOD, though we do know that it has a significant hereditary component, and is often transmitted from mother to daughter . We also know that the characteristic polycystic ovary emerges when a state of anovulation persists for a length of time. Patients with PCO have persistently elevated levels of androgens and estrogens, which set up a vicious cycle. Obesity can aggravate PCOD because fatty tissues are hormonally active and they produce estrogen which disrupts ovulation . Overactive adrenal glands can also produce excess androgens, and these may also contribute to PCOD. These women also have insulin resistance ( high levels of insulin in their blood, because their cells do not respond normally to insulin).
Fig 2. The self-perpetuating vicious cycle of elevated levels of androgens and estrogens in PCOD
While some women with PCOD will have all the classic symptoms and signs, many have what we call "occult PCOD". This means that they may be thin, have regular periods , no hirsutism and normal looking ovaries on ultrasound, but still have PCOD. This problem is detected only when these patients are superovulated, at which time they over-respond by producing a large number of follicles.
Interestingly, many of these patients present with recurrent pregnancy loss ( recurrent miscarriages) , and often their doctor does not make the correct diagnosis for them.
Treatment of PCOD for the infertile patient will usually focus on inducing ovulation to help them conceive.
For many patients with PCOD, weight loss is an effective treatment - but of course, this is easier said than done! Look for a permanent weight loss plan - and referral to a dietitian or a weight control clinic may be helpful. Crash diets are usually not effective.
Increasing physical activity is an important step in losing weight. Aerobic activities such as walking, jogging or swimming are advised. Try to find a partner to do this with, so that you can help each other to keep going.
The drug of first choice for women with PCOD today is metformin ( this medicine is also used for treating patients with diabetes. ) Doctors have now learned that many patients with PCOD also have insulin resistance - a condition similar to that found in diabetics, in that they have raised levels of insulin in their blood ( hyperinsulinemia) , and their response to insulin is blunted. This is why some patients with PCOD who do not respond to clomiphene are treated with antidiabetic drugs, such as metformin and troglitazone. Studies have shown that these drugs improve their fertility by reversing their endocrine abnormality and improving their ovulatory response.
In the past, the drug of first choice used to be clomiphene; this may be combined with low-doses of dexamethasone, a steroid which suppresses androgen production from the adrenal glands. Just taking clomiphene is not enough , and you need to be monitored (usually with ultrasound scans) to determine if the clomiphene is helping you to ovulate or not. The doctor may have to progressively increase the dose till he finds the right dose for you. If clomiphene does not work, a newer anti-estrogen called letrozole (which is also used for treating women with breast cancer) can be used. Clomiphene resistant PCO women may need ovulation induction with HMG (gonadotropins). Some doctors prefer to use pure FSH for inducing ovulation in PCOD patients because they have abnormally high levels of LH.
Ovulation induction can often be difficult in patients with PCOD , since there is the risk that the patient may over-respond to the drugs, and produce too many follicles, which is why the risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy is often increased in patients with PCOD. The doctor has to find just the right dose of HMG ( called the threshold value ) in order to induce maturation and release of a single , or only a few follicles , and this can sometimes be very tricky.
Difficult patients may also need a combination of a GnRH analog (to stop the abnormal release of FSH and LH from the pituitary) and HMG to induce ovulation successfully.
A recent treatment option uses laparoscopy to treat patients with PCOD. During operative laparoscopy, a laser or cautery is used to drill multiple holes through the thickened ovarian capsule. This procedure is called laparoscopic ovarian cauterisation or ovarian drilling or LEOS ( laparoscopic electrocauterisation of ovarian stroma) . This should be reserved for women with PCOD who have large ovaries with increased stroma on ultrasound scanning. Destroying the abnormal ovarian tissue helps to restore normal ovarian function and helps to induce ovulation. For young patients with PCO ovaries on ultrasound, if clomiphene fails to achieve a pregnancy in 4 months time, we usually advise laparoscopic surgery as the next treatment option. This is because LEOS helps us to correct the underlying problem; and about 80% of patients will have regular cycles after undergoing this surgery, of which 50% will conceive in a year's time, without having to take further medication or treatment. Having regular cycles without having to take medicines each month can be very reassuring to these patients !
The skill of the surgeon plays a key role in determining the outcome of the surgery . It is important that the surgeon selectively destroy only the stroma, and NOT the cortex. The cortex of the ovary contains the eggs, and if this damaged, then ovarian function is jeopardised, so that the surgery may actually end up causing infertility ! An additional risk of this surgery is that it can induce adhesion formation, if not performed competently.
In the past, doctors used to perform ovarian surgery called wedge resection to help patients with PCOD to ovulate. The removal of the abnormal ovarian tissue in the wedge breaks the vicious cycle of PCOD, helping ovulation to occur . While wedge resection used to be a popular treatment option, the risk of inducing adhesions around the ovary as a result of this surgery has led to the operation being used as a last resort.
For patients who do not respond to the above measures, ovulation induction plus intrauterine insemination is the next step.
If 3 cycles of IUI have failed, then IVF is the best treatment option for patients with PCOD. However, many IVF clinics have little experience in superovulating these women, and they often mess up their superovulation. Because these women grow so many eggs in response to the HMG injections used for superovulation, and because doctors are very worried about the risk of ovarian hyperstimulation, they often end up triggering egg collection with HCG when the eggs are immature. They consequently get lots of eggs, but since most of these are immature, fertilization rates and pregnancy rates are very poor.
In our clinic, because we have extensive experience in dealing with women with PCOD (which is much commoner in the Middle East and South India than in the West), we do a much better job at getting these women to grow many mature eggs. Also, because we carefully and meticulously flush each and every follicle at the time of egg collection, the risk of PCOD patients developing ovarian hyperstimulation in our clinic has been virtually zero in the last 8 years.
The good news is that with the currently available treatment options, successful treatment of the infertility is usually possible in the majority of patients with PCOD.