Ovulation Induction and PCOS: What You Should Know

Although most women with PCOS are able to naturally conceive by making lifestyle modifications - some women might need ovulation induction medications to help them conceive successfully. But what is ovulation induction and what are your options?

Posted on February 19, 2022 ·

BY Team Veera

Medically Reviewed

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Around 70% of women with PCOS experience some difficulties in becoming pregnant. A range of PCOS related factors may decrease fertility such as increased hormone levels, increased weight (BMI higher than 31) and lifestyle influences. However, medical and lifestyle management can increase the chances of a successful pregnancy.

How PCOS affects ovulation?

Ovulation is when a mature egg is released from the ovary. The egg travels to the fallopian tube, where it can  be fertilized by a sperm. If the egg is fertilized, the resulting embryo travels to the uterus, a journey that takes several days. If the embryo implants, you’re pregnant. If it doesn’t, you’ll have your “period.”  

In women with PCOS, ovulation may not occur every month, which means the egg is not released on a regular basis. Ovulation can either entirely stop (anovulation) or occur irregularly (oligo-ovulation). This makes it difficult for women with PCOS to get pregnant because either there is no egg released to undergo fertilisation.

Some women with PCOS may experience reduced fertility or ‘sub fertility’, where it might take longer to conceive, or they might need further medical assistance to achieve a pregnancy.

What is ovulation induction?

If lifestyle changes and weight loss have not helped improve your fertility after 12 months, then your doctor might recommend referral to a fertility specialist for treatment. 

Ovulation induction is a treatment, using tablets or injections, to stimulate the ovary to increase egg production. Ultrasounds and blood tests are performed to determine the best time to trigger ovulation.

Once ovulation has been triggered, semen (sperm) is introduced either by sexual intercourse or inter-uterine insemination (IUI). IUI is when collected semen is placed directly into the uterus through the cervix.

How does ovulation induction work?

For women who are not ovulating or who have irregular menstrual cycles or unexplained infertility, ovulation-inducing medications are often the first method physicians will try to achieve pregnancy. Medications stimulate the release of hormones that drive egg production. 

There are two types of ovulation induction medications – oral and injectable medication.

Letrozole

Aromatase inhibitors are ovulation-inducing tablets. Letrozole is the most widely used ovulation-inducing tablet. It is one of the options for improving fertility in women with PCOS.

An advantage is that they are less likely to result in a multiple pregnancy (twins, triplets).

Letrozole is used early in the menstrual cycle to stimulate growth and release of eggs from the ovary. The eggs potentially can then be fertilised through natural means. It can be used initially for treating infertility or, most commonly, after clomiphene citrate where women have not responded to therapy.

Side effects

There have been multiple studies of letrozole. To date, side effects include temporary gastrointestinal side effects (nausea, abdominal bloating, vomiting) and loss of appetite, tiredness, hot flushes, headache and back pain.

There were initial concerns that letrozole might increase abnormalities among babies. Current studies do not support this. However, we cannot be 100% sure of this as studies to date have not included many thousands of pregnancies, and most of these abnormalities are rare.

Clomiphene citrate

Clomiphene citrate (Clomid) is a tablet that is the most common medication used for ovulation induction. It is often recommended for improving fertility in women with PCOS who are infertile because they do not ovulate.

Clomiphene citrate is used early in the menstrual cycle to increase the chances of an egg being released by the ovary, enabling the egg to be fertilised naturally. It can be used either by itself or in combination with other drugs (eg, insulin sensitisers such as metformin) to increase its effectiveness

Side effects

It can be associated with a higher risk of multiple births (twins, triplets) as more than one egg often develops

There is a small but increased risk of ovarian cancer associated with its long-term use, so it should be used only in the short term (no longer than six to nine months)

Not all women with PCOS are responsive to clomiphene citrate, and some might have to use combinations of clomiphene with other drugs (such as metformin) to gain the most benefit.

If pregnancy does not happen within six ovulatory cycles (six months) with clomiphene citrate, your doctor will discuss other options with you.

Metformin

Metformin can be used for treating infertility in women with PCOS who don’t ovulate and who have no other reasons for infertility.

Metformin helps to improve the function of circulating insulin, and can reduce the production of androgen in the ovaries. This can improve the function of the ovaries and their ovulation rate

Metformin can be combined with other medications (such as clomiphene citrate) if women aren’t responding to those medications or if they are obese

Side effects

Some women who take metformin have some temporary gastrointestinal side effects (nausea, abdominal bloating, vomiting and loss of appetite). Metformin treatment can be started at lower doses to reduce the severity of these side effects

There are currently no guidelines for the use of metformin during pregnancy, and the usual recommendation is to stop metformin once pregnancy is achieved, unless your doctor advises otherwise.

If oral medications are unsuccessful, injectable medications such as a follicle-stimulating hormone (FSH) are typically the next step. The treatment cycle begins with an ultrasound and bloodwork on day three of the menstrual cycle. Injectable medications are started on day three and are continued for six to 10 days, depending on response. The medication is injected and the ovary carefully monitored by ultrasound to avoid over-stimulation

Gonadotripins

Gonadotropins are hormones involved in regulating ovulation, these include follicle-stimulating hormone (FSH), luteinising hormone (LH), human chorionic gonadotropin (hCG).

They are natural hormones made by the body to regulate ovulation, but they can be used also for medically treating infertility. They are generally used where women have not had success with aromatase inhibitors, clomiphene citrate or metformin.

These hormones can be used as treatments to stimulate the growth and release of eggs

Side effects

Women using gonadotropins are more likely to have multiple pregnancies or ovarian hyperstimulation syndrome – dosage is carefully regulated to reduce the risk

Although most women do not have significant side effects from the oral or injectable medications, some may experience hot flashes, mood swings, bloating, breast tenderness, pelvic pressure, abdominal pain or nausea.

It is encouraging to know that women with PCOS have been shown to have a similar number of children (with or without treatment) as women without PCOS. The recommendation, if it is desirable and possible, is to consider planning a family early. This way, if you have difficulties in conceiving, you have time to consider a range of fertility treatment options before the risk of age-related infertility begins to increase (around the age of 35).

Disclaimer: Content on Veera is provided for informational purposes only and is not intended as medical advice, or as a substitute for medical advice given by a physician

Verified by Dr. Iris Lee

Fellow in Reproductive Endocrinology and Infertility, University of Pennsylvania

Dr. Lee is a fellow in reproductive endocrinology and infertility at the University of Pennsylvania. She completed medical school and residency training at the University of Pennsylvania as well. Her work focuses primarily on PCOS, particularly the metabolic and mental health implications. Outside of work, she enjoys baking, reading, and spending time with her husband and two puppies.

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