Follistim AQ Risks, Warnings, and Complications

Note: Follistim AQ should be used only under the supervision of physicians who are experienced in infertility treatment. This drug is a potent gonadotropic substance that can cause complications such as multiple births and ovarian hyperstimulation syndrome (OHSS) as well as lung and blood vessel problems. Additionally, treatment with gonadotropins should be taken only when appropriate monitoring facilities are available.

Some of the risks of Follistim AQ use include:

• Abnormal Ovarian Enlargement: Follistim AQ can lead to abnormal ovarian enlargement. Treatment with this drug is therefore individualized, and the lowest effective dose is used. If you have significant ovarian enlargement after ovulation, your healthcare provider may prohibit sexual intercourse due to the danger of hemoperitoneum (bleeding into the peritoneal cavity) from ruptured ovarian cysts.

• Ovarian Hyperstimulation Syndrome (OHSS): OHSS is different from uncomplicated ovarian enlargement. This condition can progress quickly and become serious. It is characterized by significantly increased vascular permeability (leaking from blood vessels), resulting in the accumulation of fluid in the abdominal and chest cavities. 

  Early warning signs of OHSS include severe pelvic pain, nausea, vomiting, and weight gain. Other symptoms can include stomach pain, bloating, distention, vomiting, diarrhea, difficulty breathing, and reduced urination. OHSS occurs after Follistim AQ has been discontinued and can develop rapidly, reaching its peak 7-10 days after treatment. 

  Most of the time, it resolves spontaneously when menses start. If there is evidence of OHSS after Follistim AQ therapy, your doctor will withhold hCG administration for ovulation induction. Rarely, OHSS can be more severe and prolonged (if pregnancy occurs) and may require hospitalization. You will be assessed for development of OHSS for at least 2 weeks after hCG is administered. If you develop serious OHSS, gonadotropins, and hCG may need to be discontinued, and you may require hospitalization. 

  Clinical trials have shown that OHSS occurs in approximately 6-8% of women following Follistim AQ treatment. 

• Pulmonary and Vascular Complications: Gonadotropin treatment has been linked to serious lung complications including atelectasis (collapse of the lung), acute respiratory distress syndrome, and asthma exacerbation. In addition, gonadotropins can also cause thromboembolic events (blood clots) in association with or separately from OHSS. Women who have pre-existing risk factors for blood clots, such as severe obesity, a personal or family history, or bleeding disorders, are at an increased risk of these complications. 

  Blood clots can result in venous thrombophlebitis (vein inflammation), pulmonary embolism (blood clot in the lung), cerebral vascular occlusion (stroke), arterial occlusion resulting in limb loss, and rarely, myocardial infarction (heart attack). These complications of gonadotropins can be fatal. Your healthcare provider will carefully weigh the benefits versus risks before prescribing Follistim AQ to you.

• Ovarian Torsion: There are reports of ovarian torsion after administration of Follistim AQ. This is a condition in which the ovary twists over on its supporting ligaments. Risk factors include pregnancy, OHSS, prior history of ovarian torsion, ovarian cysts, polycystic ovaries, and prior abdominal surgery. Ovarian torsion can damage the ovary due to reduced blood supply. Early diagnosis and de-torsion is important to limit this damage. You should seek emergency medical attention for signs and symptoms such as severe pelvic pain, nausea, and vomiting.

• Multiple Births: Multiple eggs, multiple follicles, multifetal gestation, and multiple births have been reported with Follistim AQ and other gonadotropin treatments. Your healthcare provider will counsel you about this risk before starting Follistim AQ therapy.

• Congenital Malformations: Compared to spontaneous conception, the incidence of congenital malformations is slightly higher after assisted reproduction technologies such as IVF or ICSI. This may be due to parental characteristics such as sperm quality and maternal age. It may also be linked to multifetal gestations that can occur with IVF or ICSI. There is no evidence that taking gonadotropins with assisted reproductive technology (IVF or ICSI) results in an increased risk of congenital anomalies.

• Ectopic Pregnancy: Infertile women undergoing IVF and ICSI may have tubal abnormalities, which can increase the risk of ectopic pregnancies (implantation of a fertilized egg outside the uterus, typically in the fallopian tube, also called a tubal pregnancy). Your doctor will confirm an intrauterine pregnancy with β-hCG testing and a transvaginal ultrasound.

• Ovarian Neoplasms: There are rare reports of benign and malignant ovarian neoplasms in women who underwent controlled ovarian stimulation with multiple drug regimens. However, it is unclear if gonadotropins were the cause of these neoplasms.

• Spontaneous Abortion: There is an increased risk of miscarriage or spontaneous abortions with gonadotropin therapy. However, it is unclear if gonadotropins are the cause. The increased risk may be associated with the underlying infertility.

• Monitoring with Imaging and Laboratory Tests in Women: Treatment with Follistim AQ only results in follicular growth and maturation. To induce ovulation, human chorionic gonadotropin (hCG) is necessary. Your doctor will clinically assess for sufficient follicular maturation and decide on the timing of hCG administration based on an ultrasound examination of your ovaries and endometrial lining and serum estradiol levels. This is also helpful in minimizing the risk of OHSS and multifetal gestations.