Thanks to the many breakthroughs in fertility treatment in recent years, today’s women and men have a variety of fertility medications and treatment options to discuss with their doctors. At Michigan Reproductive Medicine, we believe in fully explaining each available option, and then developing a treatment customized and most cost-effective to a couple’s individual diagnosis and circumstances.
To help you get started, here is an overview of the many types of fertility medications and treatments available to meet your medical needs. Should you have any questions, please do not hesitate to set up an appointment for a consultation.
The majority of women and men struggling to overcome infertility in the U.S. (85 to 90 percent), are treated with conventional therapies such as medical or surgical treatment, as opposed to IVF or assisted reproductive technology (ART), according to the American Society of Reproductive Medicine (ASRM).With improved success in ART, surgical treatments are chosen less often.
What this means is that there are a wide range of choices for treatment, both medical and surgical, for you and our doctors to discuss. The choice of which fertility medications and treatment to choose should be based on your individual circumstances.
Although you will discuss this more fully with our doctors, here is an overview of the fertility medications used to treat disorders of ovulation and infertility:
What Fertility Medication Choices Are Available?
These medical treatments do not involve surgery and are often the most appropriate first choice for men and women who have not been able to conceive. The comprehensive evaluation of both partners’ medical history and condition by our MRM team will help to determine which treatment is most likely to bring about a healthy pregnancy for you.
Here are some of the common conditions and medical treatments that we will discuss with you:
- Clomiphene Citrate (Clomid®)
- Letrozole (Femara®)
- Gonadotropins (Bravelle®, Follistim®, Gonal-F®, Menopur®)
- Ganirelix®
- Cetrotide®
- hCG (Ovidrel®)
- Lupron®
Inducing Ovulation
The most commonly used ovulation induction agents are letrozole (Femara®), clomiphene citrate (Clomid®) and gonadotropins.
Clomiphene Citrate (Clomid®)
- How was clomiphene discovered and how does it work? It is an orally active anti estrogen agent taken in pill form. It is an artificially created chemical whose structure is very similar to that of estrogen, but it acts to block estrogen’s effect. It was developed in 1950s intended to be an oral contraceptive. However, when it was given to rabbits, the opposite effect occurred: the litter sizes of bunnies got bigger…oops! It fools the brain into not sensing estrogen and responding as though estrogen levels and ovarian function are low, when in fact it is not the case. It’s a “head fake” in sport terms. The brain responds by releasing increased amounts of the natural fertility hormone, follicle stimulating hormone (FSH), from the pituitary gland which in turn stimulates the ovaries to recruit and release eggs and potentially more than one egg at a time. By 1967, clomiphene was approved for use in the United States by the Food and Drug Administration (FDA) with the opposite intention— a fertility drug!
- How do you take clomiphene? Clomid® treatment usually begins at the start of the menstrual cycle, with the patient taking five days of pills.The lowest dose that results in ovulation is the dose of choice.
- How effective is clomiphene therapy? With Clomid® use by appropriate patients, approximately 70 percent ovulate and up to 40 percent may conceive within the first three cycles. The patient should ideally undergo no more than three failed Clomid® cycles before proceeding with an alternative treatment plan. Clomiphene can be used with ovulation induction and timed intercourse or timed intrauterine insemination (IUI) and with minimal stimulation IVF (Mini-IVF).
- Are there any side effects with Clomid®? Yes! Consider clomiphene like a double edged sword: one edge offers the fertility advantage of inducing release of an egg while the other edge may impair fertility with anti estrogen effect. It can impair your mood promoting depression, mood swings and anxiety. We recommend avoiding this fertility medication if a woman or man has a known tendency to high anxiety and depression. Their life partners may need to wear extra armor to also endure these side effects! Additional side effects may include headaches, blurred vision, and significant weight gain with higher doses and prolonged use (more than 3 months). The scientists were correct estimating clomiphene had anti estrogen effects that can impair fertility with thickening of the cervical mucus that may impair sperm transport, thinning of the uterine lining that may impair embryo implantation, delay of movement of sperm, egg and embryo through the fallopian tubes and even delay of ovulation. These fertility reducing side effects become more evident as the dose of clomiphene increases, particularly at doses exceeding 100 mg/day (2 pills/day). Clomiphene clears a woman’s body about 54 days after the last dose. Thus, there is a carry over effect of clomiphene For these reasons, our patients choosing Mini-IVF with use of clomiphene will have their embryos frozen for at least one month or longer before an embryo is placed in the uterus- sufficient time for these ill side effects on the uterus to resolve. There have no evidence that clomiphene raises the risk of birth defects to a child. There is no evidence relating clomiphene to the adverse risks of breast or ovarian cancer.
Letrozole (Femara®)
- How was letrozole discovered and how does it work? Clomiphene’s cousin is a drug called tamoxifen. Tamoxifen is a breast cancer treatment. Women with breast cancer tumors that have estrogen receptors are at risk for estrogen causing their cancer to grow and worsen. Tamoxifen blocks estrogen from reaching the estrogen receptors causing the tumors to shrink and prevent the cancer from progressing. This is a segway to the letrozole story. Letrozole is also an anti estrogen used to treat breast cancer. Instead of blocking estrogen from plugging into its receptor contained within the tumor, letrozole reduced estrogen production where ever it is being made which is mainly in the ovaries. With no estrogen around, the breast tumor shrinks. In 1997, letrozole was approved by the FDA in the United States for treatment of breast cancer. Unexpectedly, it was noticed that premenopausal women (still having eggs) who had breast cancer and were treated with letrozole were developing many large cysts on their ovaries. They were taking letrozole every single day. It was discovered that each cyst contained an egg and in fact, letrozole was causing super ovulation: the recruitment and release of an excess number of eggs. For this reason, the FDA restricted the use of letrozole to only postmenopausal women because the ovaries did not contain eggs at this time in their lives and they could not experience the side effect of super ovulation. However, like the accidental discovery of clomiphene as a fertility drug in the 1950s, Canadian scientists took the lead in the late 1990s beginning research for use of letrozole as a fertility drug. Over the next two decades we have discovered letrozole to be at least as effective as clomiphene without any of the ill side effects of clomiphene,
- How do you take Letrozole? Femara® treatment usually begins at the start of the menstrual cycle, with the patient taking five days of pills.The lowest dose that results in ovulation is the dose of choice.
- Are there any side effects with Letrozole? In 2006, there was a superb study comparing they incidence of birth defects among children born to mothers treated either with clomiphene, letrozole or no fertility medications, the last group serving as the control group. No increased risk of birth defects was observed with either clompihene or letrozole in comparison to the control group. Given that letrozole clears a woman’s body within 10 days of the last dose, it would not be present in her body by the time she became pregnant. It is no surprise that no increased risk of birth defect was observed with use of letrozole. The dose of letrozole is much less than that taken by women being treated for breast cancer and is well within the margin of safety in use. Although letrozole is approved by the FDA, its approval is limited to use in treating breast cancer. For reasons other than safety or effectiveness, the company that manufactures this medication has not pursued FDA approval for treatment of infertility. It is prescribed “off label”, but is effectively and safely prescribed and used worldwide at this time. Given that letrozole is a treatment for breast cancer, it is very unlikely that use of this medication would promote the risk of breast cancer. No observations have been reports to the contrary. No evidence has been reported to suggest an increased risk of ovarian cancer with use of letrozole.
- How effective is letrozole therapy? In 2014, a multi center study of the national Reproductive Medicine Network concluded letrozole was a more effective fertility medication compared to clomiphene for women with polycystic ovary syndrome. In 2015, the same research network concluded clomiphene was a more effective fertility medication for women who already ovulate having unexplained infertility. Even with this advantage of clomiphene, the ill side effects of clomiphene where not taken into consideration in the study leaving open the consideration that with more adverse side effects, Letrozole may still be the preferred medication for unexplained infertility. Letrozole can be used with ovulation induction and timed intercourse or timed intrauterine insemination (IUI) and with minimal stimulation IVF (Mini-IVF).
- Letrozole used in fertility preservation. Our MRM physicians also prescribe letrozole in combination with gonadotropins for women with a history of breast cancer or who may wish to recruit many eggs in advance of chemotherapy for breast cancer. Letrozole reduces the estrogen production from the ovaries thereby minimizing any worsening of breast disease that could be caused by high estrogen levels while allowing for a high number of eggs to be harvested.
Gonadotropins are fertility medications that mimic the hormones normally secreted by the pituitary gland. Gonadotropins are administered by injection. Clomiphene and letrozole stimulate the brain to produce follicle stimulating hormone within limited amounts the brain can naturally make. Taking Gonadotropin injections is actually follicle stimulating hormone and can exceed the limits of what the brain can naturally make. For this reason, gonadotropins have the potential for greater stimulation in the patient, with a greater risk for excessive follicle and egg recruitment and a greater risk for multiple fetal pregnancy. Gonadotropins may be used to induce ovulation in combination with letrozole or clomiphene or instead of either medication if a woman failed to ovulate on the oral medications. Gonadotropins can be used in conjunction with intrauterine insemination (IUI), or as part of the in vitro fertilization (IVF) procedure at MRM facilities.
Ganirelix® and Cetrotide®assist in preventing an unwanted complication of a premature LH surge that would impair egg development. These medications are administered by injection.
hCG (Ovidrel®) or Lupron® can be used to either mimic the LH surge (hCG) or trigger the LH surge (Lupron®). These medications are administered by injection.
