Clinical trial NCT02368964: IVF Treatment in Women With Immature Oocytes in Previous Cycle
Official title: Treatment for Final Follicular Maturation Induction in Patients With Previous High Ratio of Immature Oocytes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: double triggering
Oocyte maturation
GNRH Agonist
hCG
IVF treatment
immature oocytes
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-02-23
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In standard IVF stimulation cycle,human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH) as a surrogate to only the luteinizing hormone (LH) surge. Yet, the last dose of follicle stimulating hormone (FSH) is usually given between 12-24 hours before the hCG triggering dose.One protocol used at the investigators unit, after a cycle with low proportion of mature oocytes per number oocytes retrieved, is triggering with high dose hCG (500 mcg)-38 hours prior to oocyte aspiration.

Lately, new researches showed that dual triggering of final oocyte maturation with a combination of GnRH- agonist and hCG, could improve the live-birth rate of normal responders undergoing the GnRH-antagonist COH protocol

Another treatment option is high dose hCG. Only few case reports have described the use of high dose hCG after aspiration of non mature oocytes at a previous cycle. At the investigators IVF unit, patients with previous history of high percentage of immature oocytes retrieved, are triggered at the following cycle, either with double trigger or with high dose of hCG decided by the physician consulting the patient. It is still not known with which way of triggering more mature oocytes is retrieved.

The aim of this study is to perform a prospective randomized controlled study in patients with low proportion of mature-MII oocytes oocytes (\<75%) per number oocytes retrieved, despite normal response to controlled ovarian hyperstimulation ( COH ) comparing cycles triggered with high dose hCG to those triggered with hCG+GnRH agonist.

Detailed description: Patients will be prospectively randomized into two groups. The randomization will be organized through the computer. The hCG group- will be triggered for final follicular maturation with high dose hCG (500 mcg)-38 hours prior to oocyte aspiration, and the Double trigger Group- will receive gonadotropin-releasing hormone (GnRH) agonist (Decapeptyl 0.2mg) 40 hours prior to oocyte aspiration and hCG (250mcg) 34 hours prior to the oocyte aspiration. All patients will be supplemented with the same progesterone preparation( Crinone gel 8% once a day) for luteal support. Women that suffer from vaginal spotting or vaginal bleeding during the luteal phase will receive supplementation of Geston 50MG intramuscular once every 2 days.

At the day of oocyte aspiration, blood will be drawn for serum LH, FSH, estrogen (E2) and progesterone. Moreover, clear follicular fluid will be collected and tested for LH, FSH, E2 and progesterone levels.

Eligibility criteria: Inclusion Criteria:

* Patients with low proportion of mature-MII oocytes oocytes (75%) per number oocytes retrieved at the prior IVF cycle
* Age between 18-42

Exclusion Criteria:

* Women with high ovarian response:anti-mullerian hormone ( AMH) \>5, antral follicle count ( AFC) \>15
* more than 20 oocytes retrieved at the prior cycle.

Primary outcomes:
measure: Number MII oocytes per number of oocytes retrieved
timeFrame: day of retrieving the oocytes
Secondary outcomes:
measure: Total oocytes
timeFrame: day of retrieving the oocytes
measure: Pregnancy rate
timeFrame: Two weeks from induction of ovulation
measure: Number of top quality embryos
timeFrame: day of retrieving the oocytes
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba Medical Center - IVF Unit
name: Aya Mohr Sasson, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lamb JD, Shen S, McCulloch C, Jalalian L, Cedars MI, Rosen MP. Follicle-stimulating hormone administered at the time of human chorionic gonadotropin trigger improves oocyte developmental competence in in vitro fertilization cycles: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2011 Apr;95(5):1655-60. doi: 10.1016/j.fertnstert.2011.01.019.
citation: Lin MH, Wu FS, Lee RK, Li SH, Lin SY, Hwu YM. Dual trigger with combination of gonadotropin-releasing hormone agonist and human chorionic gonadotropin significantly improves the live-birth rate for normal responders in GnRH-antagonist cycles. Fertil Steril. 2013 Nov;100(5):1296-302. doi: 10.1016/j.fertnstert.2013.07.1976. Epub 2013 Aug 28.
citation: Zilberberg E, Haas J, Dar S, Kedem A, Machtinger R, Orvieto R. Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes. Gynecol Endocrinol. 2015 Feb;31(2):145-7. doi: 10.3109/09513590.2014.978850. Epub 2014 Nov 11.