Wisdom from Wisot - Redbook Magazine Fertility Q & A

Wisdom from Wisot Wednesdays, Round 13! - Reprint from Redbook’s Fertility Diaries

Hello, all, and welcome back to our weekly Q&A with top fertility expert Dr. Arthur Wisot. LOTS of great questions this week, and, at the end, a follow-up to a question posed by the doctor last week. Before we get started, the doctor's disclaimer: "My answers to questions on this blog do not constitute medical advice, but are merely meant to create an educational forum for consumers. It is always best to discuss these issues with your health care provider." The good doctor's answers are below, in bold:
Question #1: Hello, Dr. Wisot. I am almost 36 years old, and I have tried Clomid and done 3.5 IUI's with injectibles, all unsuccessful (the half was one that was stopped because of too many cysts). I also had a large fibroid removed and laproscopy surgery to remove some cysts and scar tissue. I would like to try IVF, however my insurance doesn't cover any of it so it will be a real hardship financially, but I feel we need to try now before I get too old. My RE stated my issue is low ovarian reserve, my FSH level was 7 but my Estradiol levels have been pretty high. My question is, can you give some advice on what FSH levels, Estradiol & Progesterone levels would be okay for IVF and what levels aren't really worth trying? We will only have one shot at IVF and will go into debt for that one shot.

Answer: For IVF at 36, I would like to see a Day 3 FSH of under 10; probably not above 13. Estrogen levels should be under 80; ideally under 40, as a high baseline estradiol can also be a sign of ovarian reserve issues. Progesterone is not an issue because your progesterone will likely be supplemented during an IVF cycle. Another way of looking at ovarian reserve is the count of early (antral) follicles on Day 2-3. Ask your doctor to put this all in perspective for you regarding your chances.

Question #2: Dr. Wisot, I'm 35 years old, will turn 36 in March. I've been TTC since Oct '07 with all negative pregnancy tests. I am officially unexplained infertility. I've had 3 cycles of Femara with timed intercourse, and am on my 2nd cycle of Clomid and IUI. I've been a good responder to both Femara and Clomid. I had 4 follicles (10, 12, 13, 15mm) during my mid-cycle ultrasound on my first IUI. How many IUIs should I continue to have? And if we decide to go with IVF, what are the pros and cons of minimal stimulation IVF? Religiously, we are not certain we can go with the standard IVF. Thank you.

Answer: Generally in infertility, if a treatment is to have a good chance of working it will occur in three tries. I am seeing more couples with unexplained moving to IVF rather than injectable fertility drugs with IUI after Clomid fails because you have more control over multiple pregnancy and if three cycles of injectable fertility drugs fail, you will be facing IVF anyway. We have reduced our stimulation in recent years as we are transferring fewer embryos and in fact doing more elective single embryo transfers (SET) to avoid multiples. I don't know how you define "minimal," but your most cost-effective approach is to get pregnant in the first cycle so you need to create enough eggs to try to make that happen.

Question #3: We conceived our daughter our second month on Clomid (Month 1: 50 mg, no ovulation; Month 2: 100 mg, our daughter). I am nursing her and she is 14 months old. When she was 6 months old, I tried Clomid because we have always wanted our kids close in age (my periods hadn't returned with the breastfeeding, but we induced with provera and did Clomid 100 mg). The result was a late ovulation (Day 20) with only an 8-day luteal phase. We decided to wait to try Clomid again until she was nursing less.
However, the next month I was thrilled to ovulate on my own (albeit late–Day 28–with only a 7-day luteal phase). I have PCOS and considered that remarkable! The following month (no meds) it took me 50 days to ovulate, but my luteal phase was 13 days.
Hopeful that the ovulations and sufficient luteal phase meant increased fertility for me, we went back to the doctor and did another round of Clomid 100 mg. No dice; mid-cycle scan didn't look good and I never ovulated. We tried Clomid 100 mg again the next month and I had one 19mm follicle at my mid-cycle scan, but never ovulated it.
I’m confused. My body appeared to respond better without Clomid than with it. How did my body respond better to Clomid (at 6 months) when my daughter was breastfeeding significantly more? Since I had ovulated on my own and my luteal phase became sufficient, does this mean my daughter's breastfeeding is not the interfering factor? What would you suggest we do in order to get pregnant? I am 30. Thank you so much for taking our questions! It is greatly appreciated! Have a great day!

Answer: Understanding the benefits of nursing, how about waiting until you stop completely before you use hormonal means to try to conceive? Nursing increases prolactin levels which causes poor progesterone levels and a shortened luteal phase which happened to you with the Clomid. Also what about the exposure of your daughter to the Clomid? I usually tell my patients to stop nursing before using any hormonal treatment methods. I can't explain why you are having better cycles without the Clomid but at age 30 I would not use it anyway until you wean completely.

Question #4: In June 2005 I was diagnosed with PCOS and began taking Clomid to induce ovulation so I could get pregnant. To determine if I was ovulating, my doctor had me get my progesterone level checked at CD23. I only ovulated during two of the nine cycles I took Clomid (luckily, the last cycle my gyn was willing to prescribe it, I got pregnant). Recently a friend told me there is an increased risk of ovarian cancer with taking Clomid for more than three cycles. Is there any truth to this? Would I be further increasing my chances of cancer if I were to try Clomid again?
Answer: No. That has been shown to not be true. It actually applied to all fertility drugs, but women who ever conceived had the average risk. Then they found that many of the women who never conceived had a genetic reason for the infertility which is the same as the gene for early breast and ovarian cancer. The example of this was Gilda Radner, who described in her book, It's Always Something, her embryo transfer by my partner, Dr. David Meldrum (he's the sandy-haired Protestant) and then sadly developed ovarian cancer. Her efforts led to the discovery of the BCRA-1 and 2 gene which now can be tested for. To make a long story short—you have conceived, so, "Never mind."

Question #5: Dr Wisot, thank you for taking the time to answer our questions. I probably will be asked to wean my daughter before beginning a new round of IVF. What is the reason for weaning? Is it the drugs in the breastmilk? Hormone fluctuations or uterine contractions that can occur with nursing? If ovulation (monitored by basal temps and cervical mucus) and menses are occurring regularly while I still breastfeed, can I assume normal fertility has returned? Thanks again for your insight.

Answer: This must be, "I Am Breastfeeding and Want to Get Pregnant Week." It's as I explained above; it can cause a luteal phase defect and you don't want the drugs to cross over to the baby.

Question #6: Hi. I wanted to get your opinion on embryo defragmentation as a technique to help embryo quality. On my first (unsuccessful) IVF I had three day-3 embryos transferred and they were all poor quality with lots of fragmentation. I had never heard of embryo defragmentation before, and I'm having a hard time finding any information on it. From what I understand it's a manual process done only by highly skilled labs (mine doesn't do it). But I can not find any stats, risks, indications, or other information on the internet about it, and I've only found a few IVF clinics across the country who seem to perform it based on their websites. What is your opinion of this procedure, and can you point me to any resources that I can use to research this further?
Also, do you know of any resources where I can find out about IVF studies being conducted that might pay for some/all of the procedure/drugs—a centralized website where the studies are registered or listed? Thank you so much!

Answer: Now this is a technical question. Very sophisticated; you've done your homework. The reason you can't find much on it is that there is really not a good study showing that it's effective. There is a retrospective study suggesting a benefit [Keltz, et al (Fertility and Sterility) F&S 2006; 86:321], and there is one randomized study with frozen embryos showing a benefit (Nagy ZP, et al F&S 2005; 84:1606)but these are not at the highest level of evidence. Fragments can occur when the cells divide and it's a sign of poorer embryo quality. Our embryologists do fragment removal in selected cases, but your question has inspired one of my partners when I mentioned it to him to look further into the issue so you did some good with your question. The real effort for your doctor should be to try strategies to try to improve your embryo quality if it has not already been done.
To your second question, there is no central resource which has IVF studies currently being conducted which offer some compensation for the study patients. You can call around to centers in your area and ask them if they are doing one. We are currently doing the study I mentioned in previous posts and it's a great one to join as it's an easier delivery method of progesterone and you get compensated for filling out the forms and help medical science.

And last but not least, a follow-up. Last week, Dr. Wisot asked a potential egg donor what she guessed might be the most frequent complication of egg donation. Here's her (very funny) answer, and Dr. Wisot's response:

Reader: I appreciate that Dr. Wisot assigned me homework during my winter break lol. I'll take a guess and assume that the most common complications for egg donors are pain and infection. If I'm incorrect, don't hold it against me—I'm a History major, not Pre-Med :)

Dr. Wisot: It's a good guess, but not correct. The correct answer: pregnancy in the donor. Although we instruct donors not to have relations from the start of the fertility drugs until their period after the cycle, apparently not all of them know what that means. Or maybe we should be talking to their significant others. You will make a fine history major.