Effect of ovarian stimulation on oocyte quality and embryonic aneuploidy: a prospective, randomised controlled trial
- Conditions
- SubfertilityReproductive Health and Childbirth - Fertility including in vitro fertilisation
- Registration Number
- ACTRN12616001539426
- Lead Sponsor
- niversity New South Wales - Medicine
- Brief Summary
Research question: To determine and compare the proportion of normal embryos resulting from high versus low dose ovarian stimulation protocols in an IVF cycle. Background information: IVF involves injections of FSH hormone to stimulate the ovaries to produce more eggs than usual. When higher doses of medication are used, more eggs are produced and collected. Although this may seem to improve the chances of pregnancy, some studies have shown that when more eggs are produced there might be an increase in the number of eggs that are abnormal and will go on to produce embryos that are less likely to make a healthy pregnancy. Because the answer to this important clinical question is not known, we have designed a study to test whether there is a relationship between lower and higher dose stimulation and the proportion of embryos which are abnormal. Method: Participants will be randomly allocated to one of two groups receiving different doses of FSH hormone (300 international units or 150 international units). The amount of medication prescribed to stimulate the ovaries may be changed if the response to the medication is too strong (hyperstimulation) but otherwise will remain the same throughout your cycle. Your doctor will monitor your blood tests and ultrasound results in the normal way and determine when to collect the eggs which have been stimulated. The embryos will be fertilized and then grown for five to six days as usual, to the blastocyst stage. At this point the embryology laboratory will remove a small sample of cells for genetic testing (embryo biopsy). We will test all viable embryos that are created to see whether there is a difference between the rates of abnormal embryos in each group. All embryos will be frozen (vitrified) to allow time to receive the genetic results, and only embryos which have a normal number of chromosomes will be transferred in a later cycle. Every patient will receive the same standard of care that would usually be given during an IVF cycle and the only difference between the two groups will be the amount of medication initially given to stimulate the ovaries. Participant characteristics All participants were assessed according to a strict inclusion and exclusion criteria. Of the 57 participants that were randomised, there were no significant differences in the baseline characteristics of age, weight, height and BMI between the two groups. However, the lower dose group did have on average higher serum AMH level, a blood marker used to indicate ovarian reserve in a woman. Key results: Women who were randomised to the higher dose of Menopur (300IU) on average had more eggs collected during their IVF cycle than the women who had the lower dose of Menopur (150IU) however, this did not have a significant impact on the amount of normal embryos created between the two groups. There was also shown to be a week linear relationship between the AMH level and number of eggs collected from each woman across both groups. Limitations: We report the first multicentre randomised study to explore whether the FSH hormone dose in controlled ovarian stimulation affects the proportion of embryos that were normal following IVF/ ICSI. However, it proved difficult to recruit women into the study and we fell well short of our targeted 120 participants per arm, only recruiting 57 women in total. The study was eventually terminated, after a 2-year period of recruitment, well before the required number of women could be randomised.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 57
Female age 21- 40 years (randomised before 41st birthday) and projected normal responder based on AMH 8-25 pmol/L on Roche Elecsys measurement, BMI 18.0-35. Additional inclusion criteria include: primary diagnosis of infertility (see exclusion criteria); access to ejaculated sperm suitable for IVF/ICSI (including donor sperm; see exclusion criteria re: severe male factor infertility); trying for pregnancy >12 months before randomization; regular menstrual cycles of 24–35 days; hysterosalpingography, hysteroscopy, or transvaginal ultrasound documenting a uterus consistent with expected normal function; transvaginal ultrasound documenting presence and adequate visualization of both ovaries without evidence of abnormality; the trial cycle being the first or second COS cycle ever or the first or second COS cycle after having achieved pregnancy in a previous COS cycle.
Those not meeting the inclusion criteria plus patients with significant pre-existing physical or mental health condition inconsistent with ART, unable to give fully informed consent to participation, requiring PGD for single gene disorders or parental chromosomal abnormalities. Additional: Women with polycystic ovaries (defined as ovarian volume > 10 mL or > 25 follicles per ovary) or endometrioma >2 cm diameter, severe male factor defined as <1million/mL total number sperm per ejaculate; poor response in a previous COS cycle, defined as either >16 days of gonadotropin stimulation, cancellation due to limited follicular response, or development of fewer than four follicles >15 mm; severe ovarian hyperstimulation syndrome (OHSS) in a previous COS cycle; history of recurrent miscarriage; current or past (up to 12 months before randomization); abuse of alcohol or drugs; intake of more than 14 units of alcohol per week during the past month or smoking more than ten cigarettes per day within 3 months before randomization. Use of adjuvants recorded and discouraged.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method