Polycystic Ovarian Disease - PCOD
Polycystic ovarian syndrome ( PCOS), also known as PCOD ( polycystic ovarian disease) is one of the commonest causes of infertility. Patients have multiple small cysts in their ovaries that occur when the regular changes of a normal menstrual cycle are disrupted. The ovary is enlarged; and it produces excessive amounts of androgen and estrogenic hormones. This condition is also called Polycystic Ovarian Syndrome (PCOS) or the Stein-Leventhal Syndrome.
Polycystic ovarian syndrome ( PCOS), also known as PCOD ( polycystic ovarian disease) is one of the commonest causes of infertility.
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 it 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.
PCOD 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 the "sin of diagnostic greed " ! Not all patients with PCOD will have all or any of these symptoms. We see many patients who have what I call "occult PCOD". They have regular cycles, but when they are superovulated, they grow lots of eggs, which is typical of patients who have PCOD.Most gynecologists ( and even infertility specialists !) often overlook this diagnosis, because they do not think of it.
This diagnosis can be confirmed by vaginal ultrasound, which shows that both the ovaries are enlarged, and the increased ovarian volume is suggestive of PCOD; 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. Typically, blood levels of hormones reveal elevated levels of androgens (a high dehydroepiandrosterone sulphate ( DHEA-S) level); a high LH level; and a normal FSH level. This reversal of the FSH:LH Ratio ( high LH levels with a normal FSH level) is typical of PCOD. Another new test which helps to confirm the diagnosis of PCOD is the blood level of AMH ( antiMullerian hormone). Patients with PCOD have high AMH levels. Many patients with PCOD will also have elevated insulin levels, because they have insulin resistance.
Fig 1. A schematic, comparing a polycystic ovary with a normal ovary.
We don't really understand what causes PCOD. However, we do 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.
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 is clomiphene( clomid) ; 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.
We 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. Studies have shown that these drugs can help to improve their fertility by reversing their endocrine abnormality and thus improving their ovulatory response.
A recent alternative to clomid is the new drug called letrozole( Femara). Letrozole, an aromatase inhibitor, which is now being increasingly used as an alternative to clomid for inducing ovulation in patients with PCOD. The dose is 2.5 mg daily for 5 days, starting from Day 3. Aromatase is an enzyme which converts androstendione ( an androgen) to estradiol, and because this action is blocked by letrozole , the estradiol level in the blood drops. ( Incidentally, it is because letrozole is an antiestrogen and reduces the estradiol level that it is used for the treatment of patients with estrogen receptor positive breast cancer ) . The resulting lower estradiol will in turn stimulate the release of increased amounts of pituitary FSH and LH, and thus stimulate ovulation. It's safe and effective; and does not have the anti-estrogenic activity which clomid does, so that the uterine lining and cervical mucus with letrozole is often better than it is with clomid. The use of letrozole for ovulation induction would be considered an off-label use in the United States, as it is not officially approved for this purpose.
If clomiphene does not work, HMG( gonadotropins, Repronex, Follistim ) can be used. 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.
In Vitro Fertilization:
If 3 cycles of IUI have failed, then In Vitro Fertilization 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.
An alternative 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) . Destroying the abnormal ovarian tissue helps to restore normal ovarian function and helps to induce ovulation. For selected young patients with PCO ovaries on ultrasound ( only those with large ovaries , many follicles and increased ovarian stroma ) , if clomiphene fails to achieve a pregnancy in 4 months' time, we tell them to consider 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 for these patients ! The risk of this surgery is that it can induce adhesion formation, if not performed competently.Another major risk of this surgery is that if it is done for PCOS patients who do not have large ovaries, the destruction of ovarian tissue this surgery causes can end up causing infertility by reducing the ovarian reserve !
In this video, you can watch Dr Anjali Malpani perform an operative laparoscopy , in which she performs drills the ovaries to treat a patient with PCOD ( polycystic ovarian disease).
This is what the surgeon sees on the video screen when operating.
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.
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.