Research
Risks of Ovulation Induction in PCOS
Learn about the risks of ovulation induction in PCOS, including OHSS, multiple pregnancies, and how to minimize complications for better outcomes.
June 23, 2025
·
10
Learn about the risks of ovulation induction in PCOS, including OHSS, multiple pregnancies, and how to minimize complications for better outcomes.
If you have PCOS and are struggling with infertility, ovulation induction can help. But it comes with risks. Here’s what you need to know:
Ovulation induction can be effective, with success rates of 70–80% over multiple cycles. However, proper planning, monitoring, and personalized care are essential to minimize risks and improve outcomes.
While ovulation induction is a proven way to stimulate ovulation in women with PCOS, it’s not without its risks. These include Ovarian Hyperstimulation Syndrome (OHSS), multiple pregnancies, and various side effects. With careful monitoring and tailored adjustments to treatment, many of these complications can be minimized. Let’s break down the main risks and how they’re managed.
OHSS is a potentially serious complication that can occur when the ovaries overreact to fertility medications. This condition causes the ovaries to swell and leak fluid into the abdomen. The PCOS Awareness Association explains:
"Ovarian hyperstimulation syndrome (OHSS) causes swelling of the ovaries, which leak fluid within the body. This condition occurs in women who receive fertility treatments that stimulate the ovaries to produce more eggs."
Women with PCOS are particularly vulnerable to OHSS because their ovaries are more sensitive to stimulation. High levels of human chorionic gonadotropin (hCG) can exacerbate this reaction, leading to abnormal vascular responses. Dr. Minoos Hosseinzadeh highlights the severity of the condition:
"OHSS can range from mild to severe, and in rare cases, it can be life-threatening."
The likelihood of moderate-to-severe OHSS is reported in about 1% to 5% of assisted reproductive technology cycles. Improved protocols have reduced the occurrence of severe OHSS to under 5%, though mild cases remain common, affecting 10% to 20% of cycles.
"At our clinic, we closely monitor patients for signs of OHSS through regular ultrasounds and blood tests. If there are indications that OHSS is developing, we can adjust the treatment protocol accordingly."
Another risk tied to ovulation induction is the increased chance of multiple pregnancies. Fertility medications, particularly clomiphene citrate and injectable gonadotropins, can lead to multiple births. For instance, clomiphene citrate is associated with twins in 5%–12% of cases, while injectable gonadotropins can result in multiples in up to 30% of pregnancies.
This heightened risk of multiples comes with its own set of challenges. Premature births, gestational complications, and health risks for both mother and babies become more likely. About 60% of multiples are born prematurely (before 37 weeks), compared to roughly 10% of singleton pregnancies. Mothers may face higher chances of gestational diabetes, preeclampsia, placental complications, and cesarean delivery. Meanwhile, infants could encounter issues like low birth weight, respiratory distress, and developmental delays.
Dr. Hosseinzadeh underscores the importance of monitoring to reduce these risks:
"We strive to minimize the risk of multiples by carefully controlling the dose of medications and closely monitoring follicle development."
In addition to more serious risks, ovulation induction can bring about a range of side effects. These include abdominal discomfort, hot flashes, mood swings, breast tenderness, nausea, headaches, fatigue, and reactions at injection sites. Dr. Hosseinzadeh notes:
"These are generally mild and often manageable with simple interventions or medications."
The emotional toll of fertility treatments shouldn’t be overlooked either. Stress, anxiety, and even depression can arise during this process. Dr. Hosseinzadeh adds:
"Patients may experience stress, anxiety, or depression due to the emotional rollercoaster of infertility treatments. It's important to acknowledge these feelings and seek support when needed."
It’s also worth noting that not all women respond to ovulation induction as expected. Some may continue experiencing irregular cycles or fail to ovulate, highlighting the need for ongoing monitoring and adjustments by healthcare providers throughout the treatment journey.
Certain factors can make complications during ovulation induction more likely. Being aware of these risks allows you and your healthcare provider to tailor your treatment plan and ensure close monitoring, which is crucial for a safer process.
Starting with high doses of ovulation induction medications or increasing them too quickly can overstimulate the ovaries, particularly in women with PCOS. This heightened response raises the chances of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies.
To address this, many healthcare providers use a "step-up" protocol. This method begins with low doses of gonadotropins, gradually increasing only as needed. The goal is to stimulate the development of one or two follicles while minimizing risks.
Underlying health issues, such as obesity and insulin resistance, can complicate ovulation induction. Insulin resistance affects a significant majority of women with PCOS - 75% of lean individuals and 95% of those who are obese.
Obesity itself is more common in women with PCOS (about 60%) compared to the general U.S. female population (35%). It not only worsens insulin resistance but also increases androgen levels, further complicating symptoms. Women with PCOS are also at a higher risk for type 2 diabetes, with a prevalence of 7.5% to 10%, compared to just 0.7% in healthy young women.
When it comes to ovulation induction, obese women with PCOS often face additional hurdles. They may respond less effectively to medications, experience poorer pregnancy outcomes, and have higher rates of miscarriage. Live birth rates are also lower for this group, especially for those with metabolic syndrome.
Encouragingly, even small reductions in weight - just 2% to 5% - can significantly lower insulin and androgen levels, improving PCOS-related symptoms.
Inadequate monitoring is one of the most avoidable risk factors during ovulation induction. Women with PCOS are particularly sensitive to fertility medications, so consistent oversight is essential.
Without regular ultrasounds and blood tests, excessive ovarian responses or the development of multiple follicles may go unnoticed. This greatly increases the risk of OHSS and multiple pregnancies. Proper monitoring allows healthcare providers to make timely adjustments to treatment.
Experienced professionals play a key role here. They must be able to identify early signs of overstimulation, adjust medication dosages as needed, or even cancel a cycle if necessary. In cases of multifollicular development, converting to IVF may be a safer alternative. Careful and consistent monitoring is crucial for reducing these risks.
While ovulation induction can be an effective treatment for women with PCOS, it’s not without risks. Fortunately, there are strategies to minimize complications and improve outcomes. A careful, individualized approach can make a big difference.
One of the best ways to reduce risks is by starting with the lowest effective medication dose and adjusting it gradually based on your body’s response. This approach helps lower the chances of ovarian overstimulation while still working toward successful ovulation.
For Clomiphene Citrate, the standard starting dose is 50 mg daily for 5 days. If ovulation doesn’t occur, the dose is typically increased by 50 mg in subsequent cycles. However, doses above 150 mg rarely improve success rates, and anything over 200 mg is generally ineffective. Clomiphene citrate works well for many women, inducing ovulation in about 80% of appropriately selected patients. For those who conceive, the likelihood of twins is about 5–8%.
A more efficient alternative is the "stair step" method. This involves using ultrasound monitoring between days 11 and 14 to identify women who don’t respond to the initial dose. If no dominant follicle is observed, the dose is immediately increased by 50 mg, followed by another ultrasound a week later. This method has been shown to significantly improve ovulation rates - 64% at 100 mg compared to just 22% with the traditional approach - and shortens the time to ovulation by 32–53 days.
For Letrozole, starting with 2.5 mg for 5 days often leads to suboptimal results. A 2014 study involving 750 PCOS patients found that only 28.6% ovulated at this dose, with most requiring dose adjustments.
When gonadotropins are needed, the "chronic low dose" protocol - beginning with 37.5–75 IU - is preferred. This method reduces the risk of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) compared to conventional protocols.
Regular monitoring throughout treatment is essential to ensure the right dose and to track progress.
Monitoring is a key part of reducing risks during ovulation induction. Ultrasound scans between days 11 and 14 allow your healthcare provider to assess follicle development and adjust your medication dosage as needed. The goal is to trigger ovulation when follicles are 16–18 mm in size.
Blood tests also play an important role. Elevated estradiol levels can signal an increased risk of OHSS, enabling early intervention. Additionally, serum progesterone levels above 3 ng/mL between days 22 and 25 confirm successful ovulation.
This close monitoring helps your healthcare team make timely decisions, such as altering doses, canceling a cycle if needed, or switching to in vitro fertilization if too many follicles develop. It’s all about balancing safety with effectiveness.
Taking steps to improve your overall health before starting treatment can make ovulation induction safer and more effective. For women with PCOS, addressing underlying metabolic issues is especially important.
Losing just 5–10% of body weight can restore ovulation in many obese women with PCOS. Regular exercise also helps improve insulin resistance - aim for 150 minutes of moderate-intensity activity or 75 minutes of vigorous exercise per week. Pair this with dietary changes, such as reducing daily caloric intake by 500–750 calories and following a low glycemic index diet to better manage insulin levels.
Nutritional support is another key factor. Ensuring adequate levels of vitamin D and B12, particularly if you’re taking metformin, can be beneficial. Additionally, inositol supplements may help improve insulin sensitivity.
On the medical side, it’s important to address any conditions that could complicate treatment. This includes normalizing thyroid function and managing hyperandrogenism before conception, steps your healthcare provider can guide you through.
Ovulation induction has a success rate of 70–80%, with cumulative pregnancy rates reaching 70–75% over 6–9 cycles. However, understanding and managing potential risks is crucial to ensure safety during treatment.
The primary risks include ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. OHSS affects about 1–5% of IVF cycles, while the use of clomiphene can increase the likelihood of twins to 7–10%[37]. Women with PCOS face a higher risk of moderate or severe OHSS (10–12%) compared to those with normal ovaries (0–3%). Additionally, gonadotropin treatments are linked to miscarriage rates of 20–25%, higher than the general rate of around 15%.
Certain factors can elevate these risks. For example, anti-Müllerian hormone (AMH) levels above 3.36 ng/mL are strong predictors of OHSS, with a sensitivity of 90.5% and specificity of 80%. Other risk indicators include being under 33 years old, a history of OHSS, and having more than 14 antral follicles. Recognizing these factors allows for proactive strategies to minimize complications.
To reduce risks, consider these approaches:
Personalized care plays a pivotal role in achieving the best outcomes. Clinicians should evaluate factors like age, body weight, treatment history, and the duration of infertility to tailor the approach. By combining individualized planning with consistent monitoring and gradual dose adjustments, treatment can remain both safe and effective.
For more detailed, evidence-based guidance on managing PCOS and fertility treatments, visit PCOSHelp. The resource provides up-to-date research to support you throughout your journey.
Ovarian Hyperstimulation Syndrome (OHSS) is a potential side effect of ovulation induction treatments. Symptoms to keep an eye on include abdominal bloating, pelvic pain, nausea, vomiting, and rapid weight gain.
In more serious cases, you might experience significant abdominal swelling, intense thirst, dehydration, or leg swelling.
If you experience any of these symptoms, particularly if they intensify, it's crucial to reach out to your healthcare provider right away. Prompt attention can help address complications and ensure your well-being during treatment.
Weight loss and consistent exercise are crucial for enhancing the safety and success of ovulation induction in women dealing with PCOS. Shedding just 5–10% of body weight can help regulate menstrual cycles, encourage ovulation, and improve the outcomes of fertility treatments.
Physical activity also boosts insulin sensitivity and reduces androgen levels, addressing some of the hormonal imbalances tied to PCOS. By embracing healthier habits, women with PCOS can lower the risks linked to ovulation induction and increase their likelihood of a successful pregnancy.
Dealing with emotional stress or mood swings during fertility treatments for PCOS can be tough, but there are ways to navigate through it. Techniques like mindfulness meditation, light physical activities, or spending time on hobbies you enjoy can help ease stress and improve your mood. Cognitive Behavioral Therapy (CBT) is another option worth considering, as it can help address feelings of anxiety or depression tied to PCOS.
Focusing on a well-rounded diet and staying active not only benefits your body but also your emotional health. It might also help to connect with a mental health professional or join a support group - having people who understand what you're going through can make a big difference. Taking care of your mental health is just as important as looking after your physical health during this journey.
