Two Different Types of Luteal Phase Support in Natural Cycle Frozen Embryo Transfer and Its Effect on Pregnancy Rates
Study Details
Study Description
Brief Summary
The aim of the study is to compare the pregnancy rate between women treated with Gonadotropin Releasing Hormone (GnRH) agonist together with Human Chorionic Gonadotropin (HCG) and standard luteal support with progesterone following transfer of frozen embryos in in-vitro-fertilization (IVF) natural cycles.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The rate of frozen embryos transfer (FET) has increased in recent years due to a higher tendency of single embryo transfer, use of preimplantation genetic testing, and prevention of ovarian hyperstimulation.
There are different methods to prepare the endometrium for FET:
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Natural cycle (NC) - natural preparation of the body for implantation without the need for medicinal intervention.
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Modified natural cycle (mNC) - Inducing ovulation by administration of Human Chorionic Gonadotropin (HCG) trigger.
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Medical - preparation of endometrium with hormones (estrogen and progesterone).
Following embryo transfer, luteal phase support should be considered. Administration of treatment depends on the type of cycle chosen (either natural or medicated). Treatment options include progesterone, HCG and Gonadotropin Releasing Hormone (GnRH) analog - either one of them or combined. Different protocols (dosages and duration of use) with different pregnancy outcomes were explore before with inconclusive results. We wish to investigate administration of GnRH agonist+HCG vs. progesterone.
Patients included in the study will be women undergoing natural cycle FET at the IVF center in Shaare Zedek, Jerusalem, Israel. All patients will be randomly divided into two groups, each will receive a different luteal treatment support as will be detailed later. Patients demographic data and pregnancy outcomes will be collected.
Based on the clinical pregnancy rate in the prospective study by Bjuresten, et al [Fertil Steril, 2011], where a clinical pregnancy rate of 32% was found among women treated with progesterone for luteal support, and given an alpha of 5% and a power of 80%, 144 women (72 women in each group) are required in order to demonstrate a clinical pregnancy rate of 55% in the study group.
Comparison of categorical variables will be carried out using the the chi-squared test. Comparison of continuous variables will be performed using the Students t-Test or Mann-Whitney U method depending on the variable distribution (normal vs. non-normal distribution, respectively). A multivariate regression will also be conducted in order to determine which variables are significantly and independently related. Statistical significance will be defined when P values are less than 0.05
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Study group Patients will receive luteal support with GNRH agonist and HCG according to departmental protocol: Cleavage stage embryo: ET day (embryo day 2-3) - Ovitrelle 125mcg Day 3 after ET - Ovitrelle 125mcg + Decapeptyl 0.1mg Day 6 after ET- Ovitrelle 125mcg Day 9 after ET - Ovitrelle 125mcg Embryo blastocyst stage: ET day (embryo day 5-6) - Ovitrelle 125mcg + Decapeptyl 0.1mg Day 3 after ET - Ovitrelle 125mcg Day 6 after ET - Ovitrelle 125mcg |
Drug: GnRH agonist
125 mcg once at the day mentioned
Drug: hCG
dose as mentioned
|
| Active Comparator: Control group Patients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy. |
Drug: Progesterone 100Mg Vag Tab
dose as mentioned
|
Outcome Measures
Primary Outcome Measures
- Clinical pregnancy rate [up to two month after embryo transfer]
visualization of intrauterine gestational sac on ultrasound divided by number of transfers
Secondary Outcome Measures
- Overall pregnancy rate [up to two month after embryo transfer]
number positive beta-hCG divided by total number of transfers
- Implantation rate [up to two month after embryo transfer]
number of gestational sacs divided by number of embryos transferred
- Ectopic pregnancy rate [up to two month after embryo transfer]
number of ectopic pregnancy divided by number of positive beta-hCG
- Miscarriage rate [up to 20 weeks after embryo transfer]
number of non-viable before 24 weeks divided by total number of positive beta-hCG
- Live birth rate [up to 42 weeks after embryo transfer]
number of live births after 24 weeks divided by number of transfers.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Normo-ovulatory women
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Women undergoing frozen embryos transfer in a natural cycle
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Age 18-45
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BMI 18-35
Exclusion Criteria:
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Women undergoing medicated frozen embryos transfer
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Women with a BMI over 35 or under 18.
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Women with hydrosalpinges
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Women with defects or uterine malformations (congenital) or acquired such as myomas
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Egg donation and surrogacy
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Use of preimplantation genetic testing
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shaare Zedek medical center | Jerusalem | Israel | 91031 |
Sponsors and Collaborators
- Shaare Zedek Medical Center
Investigators
- Principal Investigator: Keren Rotshenker Olshnika, MD, Sharee Zedek Medical Center, Israel
Study Documents (Full-Text)
More Information
Publications
- Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25.
- Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 5;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3.
- Groenewoud ER, Cantineau AE, Kollen BJ, Macklon NS, Cohlen BJ. What is the optimal means of preparing the endometrium in frozen-thawed embryo transfer cycles? A systematic review and meta-analysis. Hum Reprod Update. 2013 Sep-Oct;19(5):458-70. doi: 10.1093/humupd/dmt030. Epub 2013 Jul 2. Erratum In: Hum Reprod Update. 2017 Mar 1;23(2):255-261.
- Le Lannou D, Griveau JF, Laurent MC, Gueho A, Veron E, Morcel K. Contribution of embryo cryopreservation to elective single embryo transfer in IVF-ICSI. Reprod Biomed Online. 2006 Sep;13(3):368-75. doi: 10.1016/s1472-6483(10)61441-1.
- Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fertnstert.2007.06.010. Epub 2007 Nov 5.
- Mackens S, Stubbe A, Santos-Ribeiro S, Van Landuyt L, Racca A, Roelens C, Camus M, De Vos M, van de Vijver A, Tournaye H, Blockeel C. To trigger or not to trigger ovulation in a natural cycle for frozen embryo transfer: a randomized controlled trial. Hum Reprod. 2020 May 1;35(5):1073-1081. doi: 10.1093/humrep/deaa026.
- Montagut M, Santos-Ribeiro S, De Vos M, Polyzos NP, Drakopoulos P, Mackens S, van de Vijver A, van Landuyt L, Verheyen G, Tournaye H, Blockeel C. Frozen-thawed embryo transfers in natural cycles with spontaneous or induced ovulation: the search for the best protocol continues. Hum Reprod. 2016 Dec;31(12):2803-2810. doi: 10.1093/humrep/dew263. Epub 2016 Oct 25.
- Weissman A, Horowitz E, Ravhon A, Steinfeld Z, Mutzafi R, Golan A, Levran D. Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen-thawed embryo transfer: a randomized study. Reprod Biomed Online. 2011 Oct;23(4):484-9. doi: 10.1016/j.rbmo.2011.06.004. Epub 2011 Jun 15.
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