FSH and LH Versus FSH Alone for Ovarian Stimulation in Non-hormone Sensitive Onco-fertility Patients
brief summary
Fertility preservation has been performed before the initiation of cancer therapy as cancer therapy is known to be toxic for ovarian function. However, recent studies have shown that ovarian function is reduced in cancer patients even before they start cancer therapy. Reduced ovarian function has been shown by these patients having fewer mature oocytes (female eggs) and lower peak levels of estradiol (a type of estrogen hormone important for fertility). Other studies have shown that in some types of cancers, cancer patients have lower levels of anti-Müllerian hormone, which is a hormone measured to assess how many eggs patient has remaining in the body. Because of these poorer fertility markers shown in cancer patients prior to therapy, some doctors and researchers believe that alternative medications for stimulating ovaries may prove to be beneficial for stimulating the ovaries during fertility preservation. Currently, luteinizing hormone injections are approved by Health Canada for patients with hypothalamic dysfunction. Hypothalamic dysfunction is a condition whereby lower levels of fertility hormones are produced because of brain dysfunction. Other reasons luteinizing hormone is used in clinical practice is in patients with poor ovarian reserve and patients who are older. Recent research studies have suggested that some oncology patients may be poor responders prior to cancer therapy because of their underlying disease. The exact reasons for this poor response are not known. However, some researchers believe it may be related to the interactions between the brain and fertility organs, similar to patients with hypothalamic dysfunction. Because of this possible similarity to patients with hypothalamic dysfunction, adding luteinizing hormone to follicle-stimulating hormone (the hormone typically used for ovarian stimulation) may be beneficial for fertility preservation. Studies have also shown improved fertility outcomes with the addition of luteinizing hormone in non-cancer patients who were previously known to be poor responders to ovarian stimulation. The clinical trial team is aiming to conduct a randomized controlled trial to evaluate the safety and efficacy of luteinizing hormone in non-hormone sensitive cancer patients (patients with cancer other than the breast, ovary or uterus).
detailed description
The proposed study is a superiority, randomized controlled trial examining the effect of FSH and rLH (Luveris) versus FSH alone on the number of mature oocytes available for cryopreservation in non-hormone sensitive onco-fertility patients. These patients include those diagnosed with malignancy other than breast, uterine and ovarian cancer.
Given that the care of oncology patients is time sensitive, a random start of the treatment cycle is the usual approach in Mount Sinai Fertility clinic, with no prior priming. The patient has a random serum levels of estrogen, progesterone, LH, FSH and HCG levels. A transvaginal ultrasound is performed as well, and the stage of the cycle is determined. Based on the stage of the cycle, gonadotropin starting time is planned accordingly.
* Early follicular phase: Gonadotropin stimulation started. A GnRH antagonist will be given once the dominant follicle measures \>1.4 cm. * Mid to late follicular phase: patients who have a dominant follicle \>1.5 cm with an E2 \>300 and a progesterone \<5 will be triggered usually with HCG (Ovidrel 250 mcg subcutaneous). After three days gonadotropin stimulation is started. * Start of luteal phase: start gonadotropin stimulation and once the dominant follicle measure \>1.4, a GnRH antagonist will be given.
Patients will be randomly assigned in a 1:1 ratio to either treatment or control group. Treatments in each of the trial arms will be as follows:
1. Treatment arm: Patients will self-administer a subcutaneous injection of Gonal-F (FSH) in addition to Luveris daily until a pre-set criteria to trigger ovulation is reached. 2. Control arm: Patients will self-administer a subcutaneous injection of Gonal-F (FSH) daily until a pre-set criteria to trigger ovulation is reached.
Transvaginal ultrasound and bloodwork monitoring is initiated to monitor the ovarian response.
Once the patient meets one of the following two criteria
1. A serum estradiol (E2) of greater than 2,000 pmol/L 2. A follicle measuring greater than 14 mm,
A daily, subcutaneous injection of a GnRH antagonist (Cetrotide or Ganirelix 0.25 mg) will be administered by the patient subcutaneously to prevent an endogenous surge in LH. Monitoring of the ovarian response will continue until there are 3 or more follicles visualized by transvaginal ultrasound with a mean diameter of ≥17 mm. Ovulation will be subsequently triggered with a subcutaneous injection of HCG or GnRH agonist depending on the managing IVF physician. Twelve hours after their trigger medication, patients will return to the clinic for standard blood work including LH and progesterone. This is a standard confirmatory blood test to confirm that an endogenous LH surge has occurred. In approximately less than 5% of cases, the GnRH-a trigger fails to elicit an optimal surge, which may require a "rescue" low-dose hCG trigger to be administered 24 hours following the initial trigger. The decision to administer a "rescue" trigger will be at the discretion of the managing IVF physician. Transvaginal, ultrasound-guided oocyte retrieval will be performed approximately 36 hours following the administration of the initial trigger.
official title
FSH and LH Versus FSH Alone for Ovarian Stimulation in Non-hormone Sensitive Onco-fertility Patients: an Exploratory Randomized Controlled Trial