Local Expert Available To Comment On Multiple Births
Ovulation Induction
Ovulation induction medications, often referred to as fertility drugs, are used to stimulate the follicles in a patient's ovaries resulting in the production of one or more eggs in one cycle. The use of medications can help pinpoint the time of ovulation, so sexual intercourse, intrauterine inseminations (IUIs) or in vitro fertilization (IVF) scheduling is optimized.
There are different levels of ovulation induction commonly used to treat infertility related to ovulation disorders, male factor or unknown causes. One method of treatment involves oral medication - clomiphene citrate (Clomid or Serophene) or letrozole (Femara) - taken in pill form for 5 days at the beginning of a cycle. For women whose only infertility problem is anovulation, up to 80% of patients will ovulate using this medication and 50% of those will conceive. Clomiphene may be combined with IUI to boost the success of the medication by placing the sperm and egg in closer proximity to each other.
The more aggressive level of ovulation induction is called superovulation. This treatment uses gonadotropins or a combination of clomiphene or letrozole and gonadotropins to stimulate the production of multiple eggs. Patients undergoing superovulation must be closely monitored with blood tests and ultrasounds. Monitoring ensures that the patient does not hyperstimulate and also helps the physician administer the correct dosage of medication so that only a few follicles develop. This is a critical step to keeping the multiple pregnancy rates low. At the end of the superovulation treatment process, a low dose hCG (human chorionic gonadotropin) may be prescribed to stimulate ovulation. Ovulation will occur between 42-48 hours after hCG. The patient is instructed to either have intercourse during this time or to come in for an IUI. Depending on the cause of infertility, the success rate per superovulation treatment cycle is approximately 6-20% based on the woman's age and medication protocol.
Ovulation Induction Risks
Two significant risks associated with ovulation induction treatment are ovarian hyperstimulation syndrome (OHSS) and multiple births. Mild OHSS is diagnosed when ovarian enlargement and discomfort are noted either after an hCG trigger shot or when pregnancy follows an ovulation induction treatment cycle. Luckily, severe OHSS exemplified by marked ovarian enlargement and accumulation of intra-abdominal fluid (ascites) is rare, occurring in less than 1% of ovulation treatment cycles. Multiple births can occur in 3-7% of those taking oral medications and in up to 25% of those using injectable gonadotropins (FSH, hMG). With the combination of both oral medications and injectables, triplets can occur in about 6% of cases.
Risk Prevention
As these conditions pose risks to both patients and the pregnancy, prevention is the best treatment. Identifying the patient at risk and modifying drug regimens are the best options. Previously, it was common to attempt ovulation treatment with clomiphene (Clomid) and if that was unsuccessful, injection treatment was recommended. Metformin therapy offers new options for patients with polycystic ovary syndrome (PCOS) to restore normal cycles when combined with diet and exercise regimens. If this treatment regimen fails, the addition of oral medications such as letrozole or clomiphene may restore normal cycles. The oral medications may be combined with injections of FSH (Bravelle, Follistim, Gonal-F) or hMG (Menopur) to improve development of the ovarian follicles and oocytes. Alternatively, low dose gonadotropins cycles starting at 50-75 units for up to three or more weeks may be successful when OHSS is a risk.
Factors considered when determining your medication regimen include patient age, response during prior cycles and weight, as well as the number of small antral follicles seen during a day 3 transvaginal ultrasound. While intuitively, it is reasonable to believe that more follicles is better, that may not always be the case. In fact, recent data suggests that despite finding a single follicle in up to 85% of letrozole treatment cycles, pregnancy rates appear to be higher than cycles using other protocols where more large follicles are recruited. Taking into account the above factors, your physician chooses your treatment protocol to recruit one to three follicles. Unfortunately, cycle design is not an absolute science and occasionally your individualized treatment plan will result in recruiting a larger number of follicles than expected.
Treatment Options
During the course of ovulation treatment, frequent transvaginal ultrasound examinations and blood testing will help your physician adjust the dose to limit your risk of complications. Coasting (withholding all medications) or the use of low dose hCG injections instead of FSH or hMG may also be beneficial. Despite these steps, the number of follicles and the estradiol rise may indicate that your risk of multiple births and OHSS are unacceptably high. Options such as conversion to in vitro fertilization (IVF), cycle cancellation or follicular reduction and IUI were the only options previously available.
Conversion to IVF is a proven safe and effective option as oocyte retrieval significantly reduces the risk of OHSS and blastocyst culture and limiting the number of embryos transferred reduces the risk of multiple births. However, IVF is costly and not financially available to all patients.
Canceling the treatment cycle and starting over with a lower medication dose or different protocol is an unfortunate outcome for anyone who has investmented time and money for treatment.
Follicular Reduction
Follicular reduction (FR) involves oocyte retrieval as done with IVF. Yet with FR, a few oocytes are left behind and an IUI is carried out. While large studies evaluating follicular reduction are not available, our experience has been that pregnancy rates are similar to IUI cycles without FR.
Options for the "extra oocytes" removed during FR include disposal or IVF with cryopreservation of the embryos that result. Oocyte vitrification (cryopreservation) avoids disposing of valuable "extra oocytes", while avoiding the expense of IVF. As part of the follicular reduction-oocyte vitrification research protocol, the cost of oocyte vitrification and thawing is covered. IVF is provided at a significantly reduced cost if the IUI does not result in pregnancy and the oocytes are thawed for a second attempt at pregnancy.
The results from the first three patients enrolled in this study have been one ongoing pregnancy from IUI after FR, a healthy singleton delivered pregnancy following oocytes vitrification, oocyte thaw and IVF and one patient with no pregnancy resulting.
Follicular reduction, oocyte vitrification and IVF should not be seen as an alternative to low dose ovulation induction cycles or IVF. Rather, as further data become available, this technique may be one more tool available to avoid canceling stimulation cycles when an excessive follicular response occurs.
Georgia Reproductive Specialists
http://www.ivf.com
View drug information on Bravelle; Estradiol; Follistim.
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