PCOS treatment in Delhi IVF

PCOS & Infertility

Affecting about 6-12% of women in reproductive age, polycystic ovary syndrome (PCOS) is a "basket" of different medical conditions, with one finding in common: polycystic ovaries (PCO). In polycystic ovaries, multiple small cysts appear along the outer capsule of the ovaries on ultrasound imaging. PCOS is often associated with infertility, because of anovulation (lack of ovulation) and amenorrhea (lack of menstruation). However, with proper fertility treatments, PCOS patients can usually get pregnant with their own eggs.

How PCOS Causes Infertility: Polycystic Ovaries

PCOS has many variations and has wide-ranging phenotypes (clinical presentations) and associated problems. However, PCOS does have one common characteristic: multiple small cysts aligned along the outer capsule of the ovaries, with an appearance of a chain of pearls on ultrasound. Those little "pearls" are the so-called preantral follicles. Antral follicles are at a very early stage of follicle (egg) maturation. In PCOS patients, follicles and eggs stop developing at the preantral follicle stage. As a consequence, women with PCOS rarely reach ovulation, in which a mature egg would be released from the ovary for potential conception.

Women with PCOS also often (though not always) do not have regular menstrual cycles. Affected women often experience prolonged periods between menstruations, a condition called oligo-amenorrhea. Anovulation and oligo-amenorrhea are frequent characteristics of PCOS. Since a woman cannot conceive without ovulation, PCOS infertility is one of the most common types of female infertility.

PCOS Leading to Diminished Ovarian Reserve Later in Life

Another major misconception about PCOS is that this condition remains static over time. It most definitely does not; various authors recently reported that the clinical expression and severity of PCOS decline with advancing age. It is not uncommon that we see patients presenting with an old diagnosis of PCOS, and after some testing, they turn out to suffer from diminished ovarian reserve (DOR) , a condition in which ovaries no longer produce a good number of high-quality eggs. At younger ages, they may have indeed suffered from PCOS with too many follicles developing at one time, but by the time they present for infertility treatment at our NYC fertility center, they have “burnt through” their egg reserve and gone on to develop diminished ovarian reserve. From a state of excessive follicle recruitment, they have transitioned into a state of abnormally low follicle recruitment.

In conducting research on the FMR1 gene , Delhi IVF Clinic described a sub-genotype of the gene, which does exactly that: women with the so-called het-norm/low sub-genotypes presents with a PCO-like ovarian phenotype at young ages, when they recruit a large number of follicles into the egg maturation process. Then they are left with DOR because of excessive early recruitment of eggs. The het-norm/high FMR1 genotype, in turn, does exactly the opposite. Women with this sub-genotype recruit their immature eggs into maturation unusually slowly at young ages, and at very advanced ages (above age 42) still have unusually good ovarian reserve.

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PCOS Diagnosis

Given the wide variety of PCOS symptoms, professional organizations have attempted to unify diagnosing criteria for PCOS in recent years. Currently, the most widely utilized criteria are the so-called Revised Rotterdam Criteria, on which the two major professional organizations in the field, ASRM and ESHRE, have agreed: Under Revised Rotterdam Criteria, a patient demonstrating at least two out of the following three criteria is diagnosed with PCOS: (1) Oligo-amenorrhea or amenorrhea; (2) hyperandrogenism (high androgens, diagnosed either by clinical symptoms or by laboratory testing): and (3) evidence of an ovarian PCO phenotype by imaging (ultrasound).

These criteria have, however, remained somewhat controversial, not the least because according to the criteria a woman can theoretically be diagnosed with PCOS without ultrasound evidence that she has PCO.

Increasingly, PCOS diagnosis is made by anti-Müllerian hormone (AMH) levels. Excessively high AMH levels characterize PCOS, though absolute cut-off levels have not been established. The likely reason is that AMH levels decline with advancing female age, and what represents excessively high levels varies with age (for further information on age-specific hormone levels, please refer to our anti-Mullerian hormone page). Clinical manifestations of PCOS also decline with advancing age.

PCOS Symptoms

Clinical characteristics of PCOS can differ greatly. For example, a widely held misconception of PCOS, even amongst physicians, is that every woman with PCOS is relatively short and obese with signs of excess male hormones (hyperandrogenism) and virilization, such as oily skin, acne, excessive facial hair, etc. In reality, only approximately 40% of women with PCOS have this kind of peripheral phenotype (appearance). Women with PCOS can also be six feet tall, model-skinny, with absolutely no sign of high levels of androgens (male hormones).

One of the most common endocrine problems in women, PCOS is now recognized not only as a hormonal problem resulting in PCOS-related infertility. Especially (though not exclusively) its hyperandrogenic form is also associated with the so-called metabolic syndrome, a combination of risk factors for arteriosclerotic heart disease and diabetes mellitus. Timely and correct diagnosis of PCOS, and its specific phenotypes, therefore, has importance not only for fertility but also for the overall health of patients.

PCOS Treatment

If the primary goal of treatment is pregnancy with PCOS, the primary effort is to induce ovulation. Because PCOS is characterized by arrest of follicle maturation at preantral follicle stages, treatment has to push the eggs past this block. Two classes of oral fertility medications can induce ovulation: clomiphene citrate (Clomid), and aromatase inhibitors (Letrozole, with brand name Femara being the most widely used). Whether either of these drugs is preferable as first-line medication has remained controversial, and is currently under investigation in a number of multicenter clinical trials.

When these oral medications don’t work, ovulation needs to be induced with a class of injectable fertility drugs called gonadotropins. Gonadotropins are more potent, produce larger numbers of follicles and, therefore, pose higher risk of ovarian hyperstimulation syndrome (OHSS) and high-order multiple births.

OHSS is the most serious maternal complication of ovarian stimulation, and the risk is especially high in PCOS patients. While a milder form of OHSS involving some minor discomfort from fluid collecting in the abdomen is much more common than a more severe form that involves severe abdominal pain and sometimes difficulty breathing, OHSS must be avoided at all cost.

When it comes to the complications in the offspring, high-order multiples is the most feared complication due to the associated risk of severe prematurity, which, in turn, is associated with severe neurological and other defects in newborns. High-order multiples should also be avoided in fertility treatments, not only for PCOS patients but for fertility patients in general.

Delhi IVF Clinic, therefore, rarely uses gonadotropins in PCOS patients who are undergoing intrauterine inseminations (IUI) or other forms of infertility treatments that do not allow physicians careful control. In contrast, in PCOS patients undergoing IVF, both complications can be greatly reduced by stimulating the ovaries carefully, puncturing all follicles including even very small ones at egg retrieval, aspirating their fluid, and controlling the number of embryos transferred. We have cautioned against using gonadotropins in established PCOS patients, and reported over 10 years ago in the journal New England Journal of Medicine that even with most careful medical supervision, high-order multiples are almost impossible to avoid in association with spontaneous intercourse and/or intrauterine inseminations (Gleicher et al., N Engl J Med 2000;343:2-7).