Gonadotropin Injection Therapy – Superovulation
Is gonadotropin therapy for me?
You may be a candidate for gonadotropin therapy if:
- You are not ovulating and you have normal or low day 3 Follicle Stimulating Hormone (FSH) and normal day 3 Estradiol levels. If your FSH level is very high, the problem is with the ovary (Diminished ovarian reserve). Treatment with additional FSH injections is unlikely to restore ovulation and donor egg IVF is often considered.
- You fail to ovulate with Clomiphene Citrate (Clomid; Serophene) – Clomiphene resistance
- You ovulate but fail to conceive with Clomiphene
- You have a thin uterine lining while undergoing Clomiphene treatment.
- Your husband is diagnosed with male factor infertility with mild decrease in sperm count; in such cases gonadotropin therapy is coupled with intrauterine insemination (IUI).
- You have been told that you have unexplained infertility.
- You are undergoing In Vitro Fertilization (IVF).
Why is the FSH level so important?
High menstrual day 3 FSH and estrogen levels may indicate a low egg number or poor egg quality (Diminished Ovarian Reserve or DOR). The number of small eggs within the ovaries (Antral Follicle Count or AFC) can be easily counted. In general a high egg is consistent with healthier eggs and a low number is consistent with lower probability of successful pregnancy outcome. Another test for ovarian reserve is the Anti Mullerian Hormone (AMH) level. Low AMH level, low egg count and High FSH or estrogen levels are predictive of poor ovarian reserve. In such cases, injectable hormone therapy or IVF are unlikely to be successful and donor egg IVF, adoption or surrogacy (your partner’s sperm is used to inseminate another woman who will be carrying the pregnancy) are often considered.
What is the appropriate type and amount of medication for me?
Generally speaking, when the problem is lack of ovulation, ovarian stimulation resulting in the development of a single follicle is ideal. The more eggs that develop, the higher is the risk of multiple pregnancies.
In cases of unexplained infertility or when utilized in conjunction with intrauterine insemination for male factor, 2-4 follicles may be optimal.
Most commonly, a dose of 75 international units (IU) of gonadotropin (FSH, HMG) is given daily and is incrementally increased every 5-6 days until the desired response is achieved; the treatment results in a cumulative pregnancy rate of 60 – 80% after 6 cycles, but also carries a risk for multiple pregnancy.
A gentler stimulation has been advocated in patients with PCOS utilizing lower gonadotropin dosage, and slower rate of increase in the medication dose. This treatment is more likely to result in the development of a single follicle (egg), lowering the risk of multiple pregnancy or severe complications such as Ovarian Hyperstimulation Syndrome (OHSS).
Women diagnosed with a hypothalamic cause for their abnormal ovulation, usually have low levels of FSH and LH and may benefit from treatment with gonadotropin preparations containing both FSH and LH (i.e. Pergonal, Humegon, Menopur or Repronex).
Obese patients may respond poorly to this treatment (poor responders) and require high dose of gonadotropins. If they are found to have high insulin level, an “insulin blocker” such as Metformin may be added to improve the likelihood of successful ovulation.
Some patients undergoing gonadotropin treatment may ovulate spontaneously and prematurely before the eggs are ready for ovulation. Treatment with GNRH agonists or antagonists (pituitary suppression) is often utilized to block premature ovulation.
How is gonadotropin therapy monitored?
- The treatment is relatively expensive and time consuming. Expect to take daily fertility hormone injections for about 8 days. During this time, you will have several ultrasounds and blood tests to help your doctor determine when you are ready for ovulation.
- Day 2-3 of cycle – You will have a pregnancy test, estradiol level and a vaginal ultrasound (Fig.1), before you are cleared to start treatment. Sometimes large ovarian cysts may be present, and treatment is postponed until the cysts resolve.
- Day 4 of hormone injections – An estrogen blood level is measured and the medication dose is adjusted accordingly.
- Day 6 of hormone injections – continue with estrogen level measurements and begin ultrasound evaluations of the number and size of the developing follicles (Fig. 2). The eggs are microscopic and are invisible on ultrasound. We can tell, however, by measuring the size of the follicles, whether the eggs are “mature” and ready for ovulation.
- The ultrasound examination also evaluates the thickness (solid white line) and pattern of the lining of the uterus (Fig.3). The lining of the uterine cavity should be at least 8 mm thick with a trilaminar (three lines) appearance. This indicates that the uterus has been optimally prepared for embryo implantation.
- HCG “trigger” is given when ultrasound shows that the largest (dominant) follicle is 16-20 mm in size and the uterine lining is at least 8 mm thick.
- Ovulation occurs about 36-40 hours after the HCG injection.
- Intrauterine inseminations (IUI) are performed 24-36 hours after the HCG shot to coincide with ovulation. After ovulation your doctor may recommend progesterone suppositories or pills to improve the likelihood of successful implantation.
- A progesterone level is measured 7 days after ovulation. A progesterone level greater than 15ng/ml is indicative of good ovulation.
- A pregnancy test is performed 14 days after ovulation, and if pregnant, progesterone therapy is typically continued for an additional 6-8 weeks.
How successful is gonadotropin therapy?
- 60% cumulative pregnancy rate after 6 cycles of treatment in patients with PCOS.
- The treatment is most successful in women who fail to ovulate with Clomiphene therapy (Clomiphene resistant).
- At Boca Fertility we have experienced a pregnancy rate of 25% per cycle and a delivery rate of 22% per cycle for all patients treated with gonadotropins and IUI.
What are the risks and complications of Clomiphene therapy?
- Multiple pregnancy – (mostly twins) occur in approximately 20% of ovulation induction cycles utilizing gonadotropin injections.
- Poor response – treatment is discontinued during IVF when there is no response or when less than 3 eggs develop. When this happens, a different stimulation protocol utilizing higher gonadotropin dose is usually advised.
- Cycle cancellation – Gonadotropin injections are discontinued and ovulation is prevented when too many eggs develop or when the estrogen level is very high, as this may increase the risk of multiple pregnancies and ovarian hyperstimulation syndrome.
- Ovarian Hyperstimulation Syndrome (OHSS) – is a potentially life threatening complication resulting from overstimulation of the ovaries. The condition is associated with ovarian enlargement, torsion (twisting) of the ovaries, weight gain, accumulation of abdominal fluid, decrease of blood volume and low blood pressure, requiring hospitalization and aggressive treatment. OHSS may occur even with mild stimulation. Fortunately, the severe form of Ovarian Hyperstimulation Syndrome is uncommon, occurring in less than 1% of patients.
Commonly used fertility medications
Injectable Gonadotropin pens – are given to help a woman produce and release healthy eggs when ovulation is a problem or to stimulate the ovaries to produce multiple eggs during Vitro Fertilization (IVF). You must be closely monitored by an experienced fertility specialist. throughout the treatment.
GnRH medications –
- GnRH agonists are used are given to suppress pituitary function during IVF and in the treatment of endometriosis or uterine fibroids. During IVF it important to prevent your own trigger to ovulation. They can be given beginning a week before your menses (long protocol). They can also be given together with the gonadotropin injections beginning on day 2-3 of cycle (micro-dose or short protocol).
- GnRH antagonists such as Ganirelix or Cetrotide are given daily, beginning on day 6 of gonadotropin injections.