A Fertility Patient’s Guide to Clomid and its Side Effects

Clomid (clomiphene citrate) is one of the most widely used fertility drugs due to its effectiveness in stimulating ovulation for women who struggle to ovulate naturally, as well as aiding couples struggling with unexplained infertility. Clomid can be used to facilitate pregnancy in couples trying to conceive on their own, and is also used in conjunction with assisted reproductive protocols such as In vitro Fertilization (IVF) and Intrauterine Insemination (IUI).

However, like all medications, Clomid comes with its own set of potential side effects. Common side effects include hot flashes, mood swings, and bloating, which can range from mild to moderate in intensity. In rarer cases, more serious side effects such as ovarian hyperstimulation syndrome (OHSS) and visual disturbances may occur/ Understanding these side effects and knowing how to manage them is essential for anyone considering or currently undergoing treatment with Clomid.

My name is Lucky Sekhon, and I am a practicing Reproductive Endocrinologist and Infertility specialist at RMA of New York. In this post, I will explore how Clomid works and is prescribed, the various side effects of Clomid, from the common to the less frequent, but more serious ones. I will also discuss the increased risk of multiple pregnancies, such as twins, which is a notable concern for many patients. Additionally, I will look into the effectiveness of Clomid in treating unexplained infertility and potential alternatives to it. By the end of this post, you will have a comprehensive understanding of what to expect when taking Clomid and how to navigate the potential challenges effectively.

How Clomid Works

Clomid functions by interacting with the body’s hormonal system to stimulate ovulation. Here’s a step-by-step breakdown of its mechanism:

Estrogen Receptor Blockage:

Clomid is classified as a selective estrogen receptor modulator (SERM). It works by binding to estrogen receptors in the hypothalamus, a crucial part of the brain that regulates hormones. By doing so, Clomid effectively tricks the body into thinking that estrogen levels are lower than they actually are.

Increased Release of Gonadotropins

The perceived low estrogen levels prompt the hypothalamus to release more gonadotropin-releasing hormone (GnRH). This, in turn, stimulates the pituitary gland to produce higher amounts of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Follicular Development and Ovulation:

Elevated levels of FSH encourage the ovaries to develop multiple follicles, each containing an egg. As the follicles mature, they release increasing amounts of estrogen, which eventually triggers a surge of LH. This LH surge is what ultimately causes ovulation—the release of a mature egg from the ovary.

How Clomid is Prescribed and Taken

Clomid is usually prescribed as a pill that is to be taken for 5 days out of each month or cycle. Typically, I will start my patients on Clomid anywhere from Day 2 to 5 of their cycle and then taking it for five consecutive days in a row. A usual starting dose is about 50 mg per day but you can titrate it upwards to 100 mg or even 150 mg per day. When a patient is undergoing a Clomid cycle, the typical monitoring of the cycle involves doing a mid-cycle ultrasound to see how someone has responded to the drug. Quite often we will do blood work at the beginning of the cycle to make sure that all the hormones are at a good baseline before starting Clomid so we can accurately measure its effect during the cycle.

Common Side Effects of Clomid

While Clomid is an effective treatment for inducing ovulation, it can cause a range of side effects. The good news is that these side effects are temporary and will go away when you stop the medication! By far, the most common side effect my patients experience is mood swings and increased irritability. In my experience, roughly 25-30% of my female patients on Clomid experience some degree of mood swings. A research study done in 1991 showed that roughly 9 out of 14 women (61%!) who were prescribed Clomid experienced mood swings of some sort. Thus, if you are experiencing mood swings or changes in temperament while on Clomid, you can rest easier knowing that both academic research and my own clinical experience has shown that this is absolutely normal and relatively common!

Hot Flashes, Bloating, Nausea and Visual Disturbances

Beyond mood swings, another common side effect of Clomid are hot flashes, which an FDA study estimated roughly 10% of women experience while on the drug. Patients often describe sudden feelings of warmth, particularly in the face and upper body, which can be uncomfortable but are usually temporary. Further, it is relatively common for women to experience bloating, breast tenderness, nausea, headaches and visual disturbances from taking Clomid.

Frequency of Common Clomid Side Effects

Side Effect	Frequency of Occurrence(%)
Hot Flashes	10
Mood Swings	~25-30
Bloating	5.5
Breast Tenderness	2.1
Nausea	2.2
Headaches	1.3
Visual Disturbances	1.5
Abnormal Uterine Bleeding	1.3

Ovarian Hyperstimulation Syndrome

While the common side effects of Clomid are generally manageable, it’s essential to be aware of the less frequent but potentially serious side effects such as OHSS. OHSS is a condition where the ovaries become excessively stimulated, leading to swollen and painful ovaries. Symptoms can include severe abdominal pain, rapid weight gain, shortness of breath, and decreased urination. However, its’ important to note that the incidence of OHSS are very rare, somewhere around 0.1% according to research studies. This is significantly lower compared to the incidence rates for other ovarian stimulation protocols used in assisted reproductive technologies (ART), where the risk can be higher due to more aggressive stimulation methods.

Risk of Multiple Pregnancies with Clomid (aka Twins!)

One of the notable risks of Clomid treatment is its impact on the likelihood of multiple pregnancies, particularly twins. Clomid works by stimulating the ovaries to produce multiple follicles, each capable of releasing an egg. This increased follicular activity boosts the chances of multiple eggs being released and subsequently fertilized, leading to a higher incidence of twin pregnancies. Studies indicate that the incidence of twin pregnancies with Clomid ranges from approximately 5% to 12%. This is significantly higher than the natural twinning rate of about 1-2% without the use of Clomid. The likelihood of triplet or higher-order multiple pregnancies is less than 1%, but it is still elevated compared to natural conception.

Natural vs Clomid-Induced Multiple Pregnancy Rates

Pregnancy Type	Natural Incidence (%)	Clomid Incidence (%)
Single Pregnancy	98	85-95
Twin Pregnancy	1-2	5-12
Triplet or Higher-Order	<0.1	<1

How Effective is Clomid in Treating Unexplained Infertility?

In terms of effectiveness, if you are using Clomid to boost your natural ovulation to treat unexplained infertility, it’s going to improve your per cycle chance of success by just a few percentage points by increasing your ovulation rate. With Clomid, the strategy is that of persistence eventually paying off. Typically when you use Clomid, you are going to this for multiple cycles and with each subsequent cycle your body starts to respond more effectively to it, thus increasing your ovulation rate. It is not uncommon for my patients to try using Clomid for up to 3 or 4 cycles before moving onto IVF. Generally, I believe that it’s worth trying Clomid for up to 6 cycles before moving onto other treatment options such as IVF.

Clomid’s effectiveness in treating unexplained fertility over time and across multiple cycles is due to a combination of factors. For one, Clomid effectively stimulates ovulation in a high percentage of women with ovulatory dysfunctions such as PCOS. Each treatment cycle gives the ovaries another chance to produce and release an egg, thereby increasing the overall chances of conception with each subsequent cycle.

Second, some women may not respond optimally to the initial dosage but show improved ovulatory response as the dosage is adjusted in subsequent cycles. This fine-tuning process helps achieve a better hormonal balance, enhancing the likelihood of successful ovulation and fertilization.

Thirdly, Clomid is effective over time because it adds a measure of consistency and predictability to a female’s ovulation, which allows both your healthcare provider and the patient in timing intercourse or an IUI more accurately. With each cycle on Clomid, we learn a lot more about a patients.

Finally, it comes down to mathematical probability. Each cycle of Clomid represents a new opportunity for conception. Even if the success rate per cycle is relatively low (e.g., 15-20%), the chances accumulate over multiple cycles. For instance, if the probability of conception is 20% per cycle, the cumulative probability increases with each additional cycle, giving a higher overall success rate over time.

Success Rates of Clomid Treatment by Cycle

Treatment Cycle	Ovulation Rate (%)	Pregnancy Rate (%)
1	70	15
2	75	25
3	80	35
4	85	45
5	90	50
6	95	60

Alternatives to Clomid

For women who have liver disease, are breastfeeding, have undiagnosed uterine bleeding or ovarian cysts, Clomid should not be taken due to the risks it poses for those with those conditions. Luckily, Clomid is but one drug that can be used to treat unexplained infertility. Another popular alternative to Clomid is a drug called Letrozole. For more information on the differences between Clomid and Letrozole, you can find out more information here.

Conclusion

Navigating the journey of fertility treatment can be both exciting and challenging. Clomid offers a promising path for many women struggling with ovulatory issues and couples experiencing unexplained fertility, helping to induce ovulation and increase the chances of conception. However, like any medication, Clomid comes with its own set of potential side effects and risks, including the possibility of multiple pregnancies.

Your journey matters, and your health is paramount. It’s important to remember that the information provided here serves as general guidance. I promise you that your situation is unique, and the decision to use Clomid should be made in consultation with your reproductive endocrinologist (RE).

You can learn more about how I use Clomid with my patients, its effectiveness and side effects in the following YouTube video made on the topic:

Follow me on Instagram to keep up to date with my fertility related posts and content where I regularly discuss medications such as Clomid and how I use them within my clinical practice.