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The Clomid Death Sentence

A few years ago I was visiting another hospital. When touring the OBGYN department, I ran across a very busy obstetrician in the middle of office hours. He was running form room to room and had a pile of charts in his hands. After her appointment, one of his patients cornered him in the waiting area and softly said, “by the way, I have not been able to get pregnant again.” Automatically, he pulled out his prescription pad scribbled a years supply of Clomid, saying, “Let me know if nothing happens in a year.” Seeing me at the last second, he said, “Actually, make it 6 months”
Needless to say I was not happy with either of his recommendations.
Giving a patient a prescription for 6 months of Clomid may be giving that woman’s fertility a death sentence.
If a woman is 39 and not getting pregnant, and she takes 6 months of Clomid, she will probably turn 40 before she starts her work-up. By the time she makes her appointment, sees the doctor, and gets her workup, it’s 6 months, maybe longer, and now it’s all too late.
It’s ok to use Clomid. I limit it to about 3 months, and there should be some workup first. I occasionally use 6 months of Clomid, but only in the case where the woman doesn’t ovulate without it. I skip Clomid in older women.

References:

This is Your Brain, This is Your Brain on clomid

Clomid (also known as Serophene) is a very valuable medication, but it can be associated with some nasty side effects.
Believe it or not, Clomid was originally devised to be used as a birth control pill. You see, it’s an anti estrogen, meaning it blocks estrogen in your body. People thought that if estrogen was blocked, pregnancy could not occur. However, the body fights back. So when you take it, it goes to your brain and your brain says “Wow, there’s no estrogen, we need to make some.” So the upper brain sends strong signals to the part of the brain called the hypothalamus, which in turn sends signals to the pituitary gland, and a larger than normal amount of FSH is produced. The FSH travels to the ovaries, and ovulation occurs.
In women who don’t ovulate frequently, this is a miracle drug. About 80% will ovulate and about 80% of those get pregnant easily.
We also use Clomid in women who ovulate like clockwork. Why? Because it does help a little. We don’t know if it helps because it creates a better ovulation, or it’s because more eggs are released. With Clomid, 50% of the time 1 egg is released, but in the other half, 2, or less frequently 3 or more, are released.
So what about those side effects? Some are physical and some are mental. Because Clomid is an anti-estrogen, it can disrupt some pretty important estrogen-dependent tissues. One tissue is the glands of the cervix that make the cervical mucus. Sometimes Clomid will thicken the mucus and this causes problems for swimming sperm. Another is the glands that line the inner uterus, the endometrium. If the lining is too thin (a subject for another day) pregnancy will not occur. An ultrasound can measure the lining, and if it looks too thin, we move away from Clomid and go to the next step.
The mental side effects include blurry vision, seeing small spots, moodiness, jitteriness and depression. Women with significant depression should not be placed on Clomid. This is a little known but important fact. An anyonomuos blogger reminded me that headaches are another side effect.
All this being said, Clomid is a drug that helps women have babies. About 15% of women have side effects, most mild.

References:

What are Your Odds?

I bet that most of you don’t know. You were never told, but you should have been. I’ll go through it now. Please understand that many of the numbers are estimates.
Let’s start with trying on your own. In the first try, if you are under about 35, it is about 30%. In the second month it goes down a little, and if you are not getting pregnant, it goes lower and lower each month. In your 13th month (after about a year of trying), it’s 3%. The reason it gets lower is that if you are not getting pregnant, there is probably a reason, and your odds were really 3% in your first month. The numbers are a little higher if you’ve had a baby. They are lower if you are older. Many people are surprised by this number, but it’s been studied again and again. The goal of fertility treatment is to increase the 3%.
Clomid with insemination is 8%, lower if you are older. FSH IUI is 20%, but only 5% in women over 40. Future writings will discuss these drugs separately. Subtract a few points without the IUI. Subtract points for low sperm counts.
To help answer the question about when to go to IVF, just look at the numbers and decide. Cost is another factor to consider. On one hand, Clomid IUI is a lot cheaper than IVF, but on the other, the cost of 3 cycles of monitored Clomid IUI can add up. Many women with a normal HSG and good sperm do a few cycles of Clomid IUI, then a few cycles of FSH IUI, then IVF. However, there are no rules about this. After hearing the odds, especially when accounting for age, some quickly go to IVF. I’ll discuss IVF pregnancy rates later.

References:

  • Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, Hill JA, Mastroianni L, Buster JE, Nakajima ST, Vogel DL, Canfield RE. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med 1999; 340(3):177-83.
  • Dankert T, Kremer JA, Cohlen BJ, Hamilton CJ, Jong PC, Straatman H, Dop PA. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod 2007; 22(3):792-7
  • Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C. Semen preparation techniques for intrauterine insemination. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD004507.

Is There Enough Sperm for IUI?

All you need is one! We’ve all said it, but the reality is that you need millions. When determining if IUI will give you a chance, I need to introduce a new number, the Total Motile Count. When we do a semen analysis we are looking for a few things: the volume, count, motility and morphology (this one will get its own blog). The semen analysis is not the whole story. We need to see how the sperm looks after we wash it. After we get sperm for insemination or IVF we need to remove the dead cells, white blood cells and seminal fluid. There are various methods for processing sperm, but they all result in a loss of sperm. And because sperm varies on how well it tolerates the washing, post process counts may be higher or lower than expected.
The more sperm we have after washing, the higher the pregnancy rates.
We like to get more than 10 million total motile sperm. This is a good number. Between 5 and 10, the pregnancy rates are lower, and the rates are much lower with less than 5.
Time for some math. If the volume is 2cc, and there are 20 million per cc, with 50% motility, there are 20 million total motile. However washing loses on average ½ the sperm, so we are left with 10 million total motile. Still not a bad number.
If we start with 2cc of 5 million with 10% motility, that’s 1 million, but ½ million after the wash: not enough.
There are in between cases. Some lowish count samples process well and we get more motile sperm than expected, and these are great for IUI.
Next time I will write about the pregnancy rates using fertility drugs and IUI, and I will answer the comment asking when to move from iui to IVF.

References:

  • Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, Hill JA, Mastroianni L, Buster JE, Nakajima ST, Vogel DL, Canfield RE. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med 1999; 340(3):177-83.
  • Dankert T, Kremer JA, Cohlen BJ, Hamilton CJ, Jong PC, Straatman H, Dop PA. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum Reprod 2007; 22(3):792-7
  • Boomsma CM, Heineman MJ, Cohlen BJ, Farquhar C. Semen preparation techniques for intrauterine insemination. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD004507.

Endometriosis: What are You Waiting For?

The last post discussed over-blowing the search for endometriosis. This post will discuss the opposite. The following is a typical example of what I see in my practice.
A woman in her late 20’s came to see me for fertility care. She had a past history of laparoscopy for mild endometriosis. It was treated, but still she could not conceive. I put her on Clomid and she got pregnant and had a baby. 3 years later she became pregnant on her own and had her second cesarean section and a tubal ligation. Now 3 years have past, and she called me with 6 months of terrible pelvic pain. The pain was the worse with her period, described as severe. She also had pain with ovulation and intercourse. I asked her to come in for a visit, and when I examined her she was very tender in the area of her cesarean section scar.
So I started asking questions. “What did your doctor do when you told him about the pain?” “He told me to take Motrin,” she said. “But you told him you couldn’t function?” “Yes, but he told me there was nothing wrong.” “Did he offer you a laparoscopy to look for endometriosis or scar tissue?” “No, he didn’t think that it was an issue.”
I was in shock. How is it that many healthy women get laparoscopies, and yet some women with a clear indication for surgery are ignored? I still don’t have an answer.
Last week I performed a laparoscopy on this woman and sure enough she had a tremendous amount of scar tissue near her c section scar. I cut it away and even in the recovery room she felt better than she did before surgery. I didn’t see much endometriosis, but I suspect her scarring was made much worse by small amounts of it.
Pelvic pain is not normal. Periods with severe pain, or pain that lasts for more that 2 days, are not normal. I don’t want anyone to get surgery that doesn’t need it, and surgery doesn’t guarantee pain relief. But when pain interferes with the quality of ones life, a laparoscopy may result in tremendous relief. In some cases, alternatives to surgery, such as hormonal therapy, may also be beneficial.

References:

  • Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984 Aug;64(2):151-4.
  • Lebovic DI; Mueller MD; Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001; 75(1):1-10.
  • Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril .2002 77(6): 1148-1155.
  • Marcoux S, Maheux R, Berube S, et al. Canadian Collaboration Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Eng J Med 1997; 377:212-22.
  • Berube S, Marcoux S, Langevin M, Maheux R, The Canadian Collaborative Group on Endometriosis. Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. Fertil Steril 1998; 69:1034-1041.
  • Giudice LC, Kao LC. Endometriosis. Lancet. 2004 Nov 13-19;364(9447):1789-99.