January 24, 2018

Clomid can help and Clomid can harm

You’ve all heard success stories of patients getting pregnant after just taking some pills. Chances are, the pill you have heard of most often is Clomiphene citrate (CC), known by brand name as Clomid or Serophene. This is usually the first medication offered to an infertile woman by her general OB or family practice doctor. RE’s also prescribe it generously. How does it work? Well, the benefit of CC is assistance with ovulation. It can help a non-ovulating woman ovulate. It can also help a woman who already ovulates on her own by improving the quality of her hormonal stimulation, thereby resulting in better ovulation, which translates to better odds of getting pregnant. However, it is far from being perfect. First of all, not all women ovulate with CC. Second of all, ovulation is just one part of the whole picture with regards to getting pregnant. There are other factors, such as the cervical mucus and the endometrial lining, which are also important. While CC is helpful with regards to initiating or improving ovulation, it can sometimes be harmful to fertility by making the cervical mucus more hostile and making the endometrial lining less receptive to implantation.

This has been suspected by RE’s for a while when we noticed that CC can succeed in inducing ovulation about 70% of the time. Yet, only about half of these patients wind up getting pregnant with just CC alone. So the ovulation problem was being fixed, but yet, we weren’t seeing anywhere near as many pregnancies as we would expect. One possibility is that these couples had multiple problems, besides just ovulation issues. Another possibility raised was that while CC was helping with ovulation, it could be hurting with other things.

So, at what locations and in what ways might CC be harmful. I gently use the word ‘might’ because for many patients, the bad effects are not significant. Remember that people are different and respond to medications differently. Don’t go throwing away your CC and angrily calling your OB. However, while CC works great for some people, in others, it fails to solve the problem, partially because of CC’s bad side. The potential harmful effects of CC on the uterine lining are supported by a study that used special ultrasound to look at uterine blood flow. They found that CC use was associated with decreased uterine blood flow. It did not actually affect the thickness of the lining, but it did lower the propensity for the lining to be that ideal “triple-layer” appearance that we all wish for.

Another area where CC can cause problems is at the level of the cervical mucus. CC can have a tendency to interfere with the formation of that favorable stretchy mucus that sperm like.

So what can you do? Bear in mind that for most people, the downside of a three month trial of CC is just a loss of three months. While you might argue that three months is critical for someone over 40 years old, I would agree, but also add that experimenting for three months is quite feasible in almost all women in their 20’s and early 30’s. Having said that, I’m also reminded of a recent experience when a patient told me that she absolutely did not want CC because she had had a bad experience with it in the past. She told me that her OB had prescribed her CC and that it had “made her gain 20 pounds.” Not only that, the stress of gaining that 20 pounds caused her to gain an additional 50 pounds. This is the only time I’ve ever encountered such a report, but it goes to remind me that every patient is different.

Anyway, back to the lining and mucus, how do you get around the potential harmful effects of CC on these areas?

With respect to the lining, my favored approach is to abandon the CC and move on to injectables, which can be very friendly to the lining. With respect to the mucus, my favored approach is to punch past the unfavorable mucus by doing simple IUI’s. So, the bottom line is that if you have successfully ovulated on CC, but are still not pregnant after three cycles, it’s time to discuss the above issues with your doctor, keeping in mind that in some cases CC is your friend and in others cases, CC can be your enemy.

  • Campbell

    Great info on Clomid. Can you comment on combining Clomid with injectables for IVF? My RE says there is evidence that taking CC in the first few days of a cycle can boost response to injectables. My egg retrievals have been relatively low (4-7) during 2 rounds of IVF with 450-600 IUs of stims.

  • IVF-MD

    I would not recommend it as first-line treatment. But if you have not gotten the results you wanted with standard injectables-only, then it’s something I might consider trying.

  • Andrea

    This is excellent information! I’ve been trying to explain this to my husband for the past few days- I think I’ll just forward this post! I also have a question. I’m so curious to know your opinion on Micro-IVF, Mini-IVF, and Eco-IVF. It’s been “sold” to me as an option, and I really enjoy your candid opinions and the way you explain things. Thanks!

  • Rachel

    I just finished my first round of Follistim and my first IUI. My doc did IUI 24 hrs and 48 hrs after the hcg injection. I had 3 follicles of good size, on Day 10 by ultrasound. Is it common to have IUI on Day 11 & 12? When I was on Clomid previously I always had the hcg and ultrasound on Day 12. Just curious, the question didn’t come to me until after the IUI’s.

  • Allie

    Sorry that this is a double post that I posted on an inactive thread.

    I’ll try to ask my question here. I have been pregnant 1x, had normal periods after the pregnancy, and then went on the pill for a year. Post pill for 7 months I was not having regular periods (one every 2 months). I don’t have PCOS, my thyroid was normal so we tried provera induction to clomid. I spotted briefly 10 days after I ended provera, and then started clomid on day #5.

    As soon as I started the clomid, I started bleeding. I was crampy and miserable, but I didn’t get the full hyperstimulation side effects people mention. I started to feel better off the clomid, but I am still bleeding now 7 days after stopping clomid. I have no idea when I’m ovulating because I’m still bleeding and it doesn’t seem to be slacking off.

    What does this mean for my future ovulation cycles?

  • IVF-MD


    Without knowing the exact details of what was happening internally (follicle growth, hormone levels), any attempts to explain what happened would only be guessing. As for your future, it’s probably fair to say that you may be at risk to have inconsistent ovulation problems on your own. But there is hope if you are able to undergo the proper treatment. Make sure you find an RE with whom you feel comfortable. Good luck!

  • CM

    What about things like baby aspirin to help with the blood flow to the lining, and Robutussin etc. to help with hostile CM?

  • IVF-MD

    People have tried those and some get pregnant and some don’t. Again, those who don’t get pregnant need to make the right decision about moving up to something more effective than just unmonitored Clomid.

  • AF


    My doctor has put me on ten days of Progesterone to jump start my period. He is then going to prescribe Clomid (while monitoring me). I am concerned that there is an underlying thyroid issue at play. I was diagnosed with thyroiditis (as a teen) and Hashimotos. My levels over the last few years have been normal- with no treatment. I have also just had my TSH tested and it came back at 2.87- which my Dr says is in the normal range of 1-3. I have read that under 2 is optimal for pregnancy.

    I should also note that my current cycle is already 55 days long and I have always had very irregular cycles. I am 35 years old.

    My concern is am I jumping the gun by going on Clomid and missing a possible thyroid issue or is my Dr correct in going this route? Is this the best solution for my issues?