The Road to Successful Ovulation In this chapter I'd like to reveal how we use the newest technologies to overcome ovulatory problems. With the use of ultrasound monitoring and "instant'' hormone assays, ovulation induction has become a science instead of a shot in the dark as it once was. The medications and monitoring techniques work so well that when you fail to get pregnant, I must suspect some other interfering and perhaps undiagnosed condition. Individualized treatment is far more effective than a preset regimen. Because of this, it is difficult for me to say, for example, that you will be given a certain dosage for so many months and then double that dosage for a certain number of months and so forth. Your doctor will determine the best course of treatment based on your unique response to the medication. I can only share with you what I do, and help you to understand my reasoning. With this knowledge you will be better equipped to understand what your doctor does and to ask questions about your particular situation. Ovulation Induction: Screening Candidates Minimum Prerequisites The minimum prerequisites for ovulation induction therapy are the same as those for fertility. The woman needs one open (patent) fallopian tube and an ovary that is able to produce mature eggs. To ensure the best possible response to the medication, all other fertility problems such as abnormal day 3 FSH or clomiphene challenge test, excess prolactin levels, endometriosis, uterine abnormalities, and inadequate sperm should be ruled out. Progesterone Withdrawal The progesterone withdrawal test will determine which ovulation induction regimen will work best for you: Clomid, Serophene (clomiphene citrate), Pergonal (human menopausal gonadotropin), or a relatively new treatment option, GnRH (gonadotropin-releasing hormone). Think for a moment about what the progesterone withdrawal test reveals. If you menstruate in response to the test, your pituitary is stimulating your ovaries to make some estrogen. In order to do this, both your hypothalamus and pituitary gland must be intact and working-at least to some extent. So by prescribing Serophene I can trick your hypothalamus and pituitary into making more LH and FSH, which will "kick" your ovaries into high gear. About 20 percent of women treated with Serophene will not ovulate. They may respond, however, to a combination of Serophene and Metrodin treatment, which I'll describe later in this chapter. If progesterone withdrawal does not cause you to have a period, I suspect a uterine abnormality or that your hypothalamus and/or pituitary cannot stimulate your ovaries to make estrogen. Once I've eliminated uterine abnormalities as your problem, you become a candidate for gonadotropin hormone replacement therapy with GnRH or Humegon/Pergonal (LH and FSH) or Metrodin (FSH). Women with low estrogen production (hypoestrogenic) respond best to gonadotropin treatment: about two thirds of them will conceive. Women with a functional pituitary may respond to GnRH. Studies suggest that using GnRH to stimulate a "natural'' pituitary hormone release may improve results as well as reduce the number of adverse side effects associated with Serophene and gonadotropin injections-hostile mucus and multiple births' for example. I'll discuss more about this technique later in this chapter. Clomiphene Citrate Therapy (Serophene/Clomid) Clomiphene citrate is available in two popular brand-name medications Serophene and Clomid. For the sake of simplicity, throughout this discussion I'll refer to either of these medications as clomiphene. Clomiphene is indicated for the woman who withdraws to progesterone and thus demonstrates an intact hypothalamus and pituitary gland. Clomiphene works by stopping up the estrogen receptors on the hypothalamus and the tricking the hypothalamus into thinking that you don't have enough estrogen In response, the hypothalamus "beats the drum'' harder and your pituitary gland produces more FSH (follicle-stimulating hormone) and LH (luteinizing hormone) which initiate follicular growth. Clomiphene Treatment Regimen The exact procedure for clomiphene treatment will differ from one couple another. Kathy and Stephen S. had a bumpy but fairly typical experience. "Dr. Perloe, before we get started could you tell me exactly how all of this is going to work?" Kathy asked. "Sure.'' I handed her the clomiphene prescription. "Before you leave I'll give you Provera pills to start your period. In less than a week or two your period should start. If it doesn't, please call me. On the third day of your cycle I want you to begin taking 50 milligrams of clomiphene-that's one pill each day for five consecutive days. Kathy tucked the prescription into her purse. "How does clomiphene make me ovulate?" "As your follicles develop, they release estrogen into your bloodstream. Normally this estrogen would tell your hypothalamus to slow down. Clomiphene, though, is masking the presence of the estrogen. Thinking, that your ovary isn't working at peak efficiency, you will continue to stimulate the growth of the follicles in your ovaries. Giving your follicles this extra boost for a few days will help them grow to maturity. When your estrogen level peaks a week or so after you stop taking the clomiphene, your pituitary gland should release a large dose of LH to free your egg from the follicle." "Do I need any blood tests", Kathy asked. "After you take clomiphene for the first time, I like to check the LH and FSH blood levels a few days after clomiphene. In some women, clomiphene brings about an increase in LH but very little FSH increase. Or the FSH level may be very high. Both of these situations mean pregnancy may be less likely and we'll need to discuss your options before proceeding." "When should we have sex?" she asked. "You should ovulate around cycle days 13 to 16. Four days after finishing the clomiphene, you can begin testing for the LH surge by using a simple urine test kit. You don't want to start checking too soon, because clomiphene causes a rise in LH which may show up on the urine test. So if you test too early you may think you are ovulating, but, in fact you may not be ready for a few more days." Call me around cycle day 16 if you have not seen a urinary LH surge. We can check an ultrasound to see if you have developed follicles and the uterine lining is ready. If so, an hCG injection can trigger ovulation. If the follicles are still small, we will increase your dose next month. If you ovulate, I will recommend that you try at least three months. If it doesn't work by then, we may choose to add hCG injections and inseminations to try and improve the pregnancy rate. I showed her to my office door. "Now, don't get discouraged if you don't ovulate the first month. It may take several cycles to find the right dosage for you. "Thank you, Dr. Perloe, I'll see you in a few weeks. Wish us luck.'' "You've got it." About a month later Kathy called to say that the progesterone had brought on her period and she had taken the clomiphene, her cycle day 9 LH and FSH were fine, but her urinary LH surge kit never changed colors. It appeared that she had not ovulated. I asked her to come in for an ultrasound. "Did I ovulate?" "Well' I'm not sure we've made that much progress. But anything is possible. I also want to do an ultrasound examination to let me look at your ovaries to see the size and number of your follicles. That will tell us if the clomiphene is doing its job.'' I picked up the smooth vaginal ultrasound wand (transducer) and gently placed it into Kathy's vagina. "Ultrasound works by bouncing sound waves off your internal organs. We use sound waves because they don't expose you to radiation. "You won't feel a thing except me pushing against your bladder and the top of the vagina.'' I centered the probe over her right ovary. "This will produce a TV picture that shows me how many follicles you're developing and what size they are." "There it is-a follicle 10 millimeters in diameter. Let's try the other side.'' When I saw just two small follicles on vaginal ultrasound, I recommended a progesterone shot so we could try again at 100 mg. "When your next period starts, I want you to increase your dose to two tablets a day." "Do you think the clomiphene is going to work?", Kathy asked. "Remember, I told you that it may take several cycles to fine-tune your dosage. If the 100-milligram dosage fails, we may decide to add a few days of Metrodin injections.'' A few weeks later, after trying two clomiphene tablets (100 mg) for five days, Kathy called and told me that her BBT chart was still "flatter than a pancake'' and her LH stick still hadn't changed. She seemed a bit discouraged, but I assured her this wasn't unusual. I recommended that she come in for another ultrasound and asked her to stop by my office for a few minutes to talk. "You think this will be the month I'll get pregnant?" I positioned the wand over her left ovary, and to my delight I found an 19 mm and 20 mm follicle and a thickened midcycle uterine lining measuring 12 mm. "Kathy, you should be having an LH spike any moment. I want you to continue testing your urine each morning. When you've had a surge, we can schedule a postcoital examination for the next morning. We need to know whether or not clomiphene is adversely affecting the quality of your cervical mucus. But, if you do not have an LH surge by Monday, I want you to have intercourse Monday night and come to the office Tuesday for a postcoital test and to give you an hCG injection. This medication should free your egg within forty-two to forty-eight hours.'' Monday morning she called to say that she had not surged and would come in for the postcoital test and the hCG injection. When I did the postcoital examination, I found that Kathy's mucus was scant and very thick. I can't say I was too surprised, since nearly half of the women on clomiphene therapy suffer from mucus problems. I explained that if she did not conceive this month, I suggested that they try intrauterine artificial insemination (IUI) with Steven's sperm. She said that she and Steven had discussed IUI and that it was all right with both of them. Kathy returned four days later for an ultrasound and a progesterone blood test to confirm that she'd ovulated. I was happy to report that I saw a large corpus luteum. Unfortunately, she did not conceive. "Don't be discouraged"' I told them. "Nearly one-third of all women taking this treatment have a poor postcoital test and many get pregnant with insemination. We'll check Kathy's ovaries and then give you another clomiphene prescription for next month. Go ahead and use the urinary LH test again. I believe we'll still have to give Kathy an hCG injection before she'll ovulate, but there's no sense in giving the hCG injection if she has an LH spike on her own. We may need to repeat the ultrasound just before midcycle because the hCG must be given at exactly the right time or it won't work. "I believe we have most of your problems under control." I leaned against the counter. "You know, it's discouraging for me, too, when a new problem shows up in each cycle. But if you look at it as tackling one problem at a time, it makes solving your fertility problem manageable. The only thing I'm still concerned about is Kathy's cervical mucus, you may want to try artificial insemination.'' The next month she repeated the procedure: 100 mg of clomiphene for five days, urinary LH test strips to detect the LH surge, ultrasound examinations until a mature follicle developed, an hCG injection to stimulate ovulation, and an intrauterine insemination. We began monitoring the development of a 16 mm follicle. When it reached 20 mm, I gave her hCG and told her to bring Steven with her the next day for IUI. "Before this is over, you are going to know as much about this process as I do." I laughed. The inseminations went well, and her BBT rise confirmed that she had ovulated and that the corpus luteum had formed. Now all we had to do was wait. If her BBT stayed up and her period did not start, we'd know she was pregnant. I guess it wasn't meant to happen-not that month, anyway. Kathy called a couple of weeks later to tell me that her period had started. "Don't worry,'' I said. "We've got you on the right routine now and it's only a matter of time. It may take three or four normal cycles before we make that baby. If you are not pregnant after finishing three cycles we need to review all your options." Each month I could tell that it was becoming harder for them to keep up their optimism. I assured them that Kathy's cycles were working fine on this regimen and that it was only a matter of time. Three weeks after their third IAIH she called me. "Dr. Perloe, I think we did it. My period is four days late." Sure enough, that month, Steven and Kathy started Jamie! Continued Return to the IVF Homepage This page, and all contents, are Copyright © 2005 by IVF.com, Atlanta, GA, USA.