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Growth hormone administration on uterine receptivity in women with recurrent implantation failure in an oocyte donation program
Last registered on July 03, 2016

Pre-Trial

Trial Information
General Information
Title
Growth hormone administration on uterine receptivity in women with recurrent implantation failure in an oocyte donation program
RCT ID
AEARCTR-0001408
Initial registration date
July 03, 2016
Last updated
July 03, 2016 9:34 AM EDT
Location(s)
Region
Primary Investigator
Affiliation
Competence Centre on Health Technologies
Other Primary Investigator(s)
PI Affiliation
Clinica MARGen, Molecular Assisted Reproduction and Genetics
Additional Trial Information
Status
Completed
Start date
2010-09-01
End date
2015-12-31
Secondary IDs
Abstract
STUDY QUESTION: Can growth hormone (GH) improve the chance of pregnancy and birth in women with repeated implantation failure (RIF) with donated oocytes?
SUMMARY ANSWER: In the context of RIF (defined as 2 failed oocyte donation attempts in this study), the administration of GH improved significantly the pregnancy and live birth rates with donated oocytes, although these success rates remained lower as compared with first-attempt oocyte donation cycles. Additionally, GH improved significantly endometrial thickness in women with RIF.
WHAT IS KNOWN ALREADY: Despite high success rates with oocyte donation, certain couples experience unexplained RIF with this approach. GH improves uterine receptivity in cows.
STUDY DESIGN, SIZE, DURATION: This was a randomized study conducted between 2010 and 2015 and comparing success rates of oocyte donation in 35 RIF patients with GH and in 35 RIF patients without GH. Results were compared with those of 35 first-attempt oocyte donation cycles (positive control).
PARTICIPANTS/MATERIALS, SETTING, METHODS: The maximum age of oocyte donors was 25 years. The age of women receiving embryos from this program (oocyte recipients) was comprised between 30 and 51 years. Oocyte donors were stimulated with the use of a long GnRH agonist protocol. Oocyte recipients were treated with progressively increasing doses of oral estradiol after previous pituitary desensitization. IVF was performed by ICSI in all cases included in this study.
MAIN RESULTS AND THE ROLE OF CHANCE: The RIF patient group receiving GH administration demonstrated significantly thicker endometrium, and higher success rates when compared to the non-GH patient group (negative control), although still lower as compared to patients undergoing their first oocyte donation attempt (positive controls). The inclusion of the negative and positive control groups reduces the role of chance in these observations.
LIMITATIONS, REASONS FOR CAUTION: The sample size in this study was sufficient to interpret adequtely the results. However, it has to be stressed that the effects of GH were studied in a very particular category of patients (RIF with oocyte donation). Hence, these observations are not applicable to most patients treated by oocyte donation. On the other hand, these results offer a new chance to patients suffering from RIF in oocyte donation programs.
WIDER IMPLICATIONS OF THE FINDINGS: Our study shows that there is a group of women with a problem of endometrial receptivity, independent of oocyte and embryo quality. GH can be useful to alleviate this condition. Even though these results were obtained in an oocyte donation program, the same problem may occur in any woman treated by IVF with her own oocytes. Further research is needed to identify patients who could benefit from getting GH treatment, independently of age and oocyte quality.
External Link(s)
Registration Citation
Citation
Altmäe, Signe and Jan Tesarik. 2016. "Growth hormone administration on uterine receptivity in women with recurrent implantation failure in an oocyte donation program." AEA RCT Registry. July 03. https://doi.org/10.1257/rct.1408-1.0.
Former Citation
Altmäe, Signe, Signe Altmäe and Jan Tesarik. 2016. "Growth hormone administration on uterine receptivity in women with recurrent implantation failure in an oocyte donation program." AEA RCT Registry. July 03. https://www.socialscienceregistry.org/trials/1408/history/9241.
Experimental Details
Interventions
Intervention(s)
This study includes in total 105 infertile couples undergoing oocyte donation program. 70 couples that experienced at least two previous failures in an oocyte donation programs tour clinic are referred to as recurrent implantation failure (RIF) patients throughout this study. Thirty five of these couples were included in the GH-treatment protocol, while the remaining 35 couples were treated in a usual way (negative control). Other 35 couples, treated in the same period and undergoing their first oocyte donation attempt, were included as a positive control group.
According to the rules of our clinic, the maximum age of all oocyte donors was 25 years. The age of women receiving embryos from this program (oocyte recipients) was comprised between 30 and 51 years. IVF was made by ICSI in all cases included in this study, as described before (Hazout et al., 2006 RBMO).
Ovarian stimulation of the oocyte donors, as well as the treatment of oocyte recipients, were carried out as as described (Tesarik and Mendoza, 2002 Hum Reprod). Briefly, oocyte donors were stimulated with the use of a long GnRH agonist protocol and a combination of human recombinant FSH (Puregon or Gonal F) and human menopausal gonadotropin (Menopur). Oocyte recipients were treated with progressively increasing doses of orally administered pure estradiol (Provames) or estradiol valerate (Progynova) after previous pituitary desensitization with a single injection of the long-acting preparation of GnRH agonist triptorelin (Decapeptyl 3,75 mg) as described (Tesarik and Mendoza, 2002 Hum Reprod).
These protocols made it possible to synchronize the ovarian stimulation of each donor with the development of the endometrium with her respective oocyte recipient. Consequently, all attempts of oocyte donation included in this study were carried out with fresh oocytes. Supernumerary embryos were cryopreserved, but results with cryopreserved embryos are not included in this study.
Intervention Start Date
2010-10-01
Intervention End Date
2015-09-01
Primary Outcomes
Primary Outcomes (end points)
Pregnancy rate, live birth rate and live delivery rate were the primary outcomes. Secondary outcomes included ongoing pregnancy rate, implantation rate and ongoing implantation rate, and miscarriage rate.
The pregnancy was defined as a positive beta-hCG test, and the ongoing pregnancy was defined as the presence of at least one fetal heart pulsation on ultrasound beyond 20 weeks. Pregnancy rate was calculated as the number of patients with positive beta-hCG test divided by the number of patients in whom embryos were transferred, while the ongoing pregnancy rate was the number of patients with the presence of fetal heart activity divided by the number of transfer procedures. Implantation rate was the number of embryonic sacs detected on ultrasound divided by the number of embryos transferred, and the ongoing implantation rate was calculated by dividing positive beta-hCG test with the number of embryos transferred. The miscarriage rate was defined as the number of miscarriages before 20 weeks divided by the number of women with a positive pregnancy test. Live birth rate was calculated as the number of babies born by the number of embryos transferred, and the live delivery rate was obtained by dividing the number of births with the number of transfers.
Primary Outcomes (explanation)
Secondary Outcomes
Secondary Outcomes (end points)
Secondary Outcomes (explanation)
Experimental Design
Experimental Design
This was a randomized study conducted between 2010 and 2015 and comparing success rates of oocyte donation in 35 RIF patients with GH and in 35 RIF patients without GH. Results were compared with those of 35 first-attempt oocyte donation cycles (positive control).
Experimental Design Details
Randomization Method
All RIF patients were informed about the potential benefits and risks of using GH in their protocol as well as about the additional cost of this treatment. Consequently, the patients were randomized into the GH and non-GH group according to their willingness to accept the new treatment suggestion. Due to the nature of the intervention, the clinician and the patients were not blinded.
Randomization Unit
Treatment protocol, GH administration or not.
Was the treatment clustered?
Yes
Experiment Characteristics
Sample size: planned number of clusters
3 different treatment groups
Sample size: planned number of observations
At least 31 women in each group, meaning that in total at least 93 women were planned to include into the study
Sample size (or number of clusters) by treatment arms
Final sample size was: 35 women with recurrent implant failure undergoing oocyte donation program, who received growth hormone treatment; 35 women with recurrent implantation failure undergoing oocyte donation program, that did not receive growth hormone treatment; 35 women undergoing their first oocyte donation program.
Minimum detectable effect size for main outcomes (accounting for sample design and clustering)
The pregnancy rate of RIF patients in oocyte donation program in our clinic has been rather low (<20%) as compared with good prognosis patients (>75%). Assuming that there is a 50% increase in pregnancy rate with GH administration (i.e. an increase from 20% to 30%), 31 subjects are required in each group to give a test of significance on 0.05, power of 90%, and standard deviation (SD) of 0.6.
IRB
INSTITUTIONAL REVIEW BOARDS (IRBs)
IRB Name
National Ethics Committee, Spain
IRB Approval Date
Details not available
IRB Approval Number
Details not available
Post-Trial
Post Trial Information
Study Withdrawal
Intervention
Is the intervention completed?
No
Is data collection complete?
Data Publication
Data Publication
Is public data available?
No
Program Files
Program Files
Reports and Papers
Preliminary Reports
Relevant Papers