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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.
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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study group | Active Comparator | Patients will receive luteal support with GNRH agonist and HCG according to departmental protocol: Cleavage stage embryo:
Embryo blastocyst stage:
|
|
| Control group | Active Comparator | Patients will receive luteal support with vaginal progesterone - 100 mg Endometrin twice daily until week 8 of pregnancy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GnRH agonist | Drug | 125 mcg once at the day mentioned |
| |
| hCG |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical pregnancy rate | visualization of intrauterine gestational sac on ultrasound divided by number of transfers | up to two month after embryo transfer |
| Measure | Description | Time Frame |
|---|---|---|
| Overall pregnancy rate | number positive beta-hCG divided by total number of transfers | up to two month after embryo transfer |
| Implantation rate | number of gestational sacs divided by number of embryos transferred |
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Inclusion Criteria:
Exclusion Criteria:
patients going in-vitro-fertility treatments with embryo transfer
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Heli Alexandroni, MD | Contact | +972549900913 | heli.alexandroni@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Keren Rotshenker Olshnika, MD | Sharee Zedek Medical Center, Israel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shaare Zedek medical center | Recruiting | Jerusalem | 91031 | Israel |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23820515 | Background | 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. | |
| 16984767 | Background |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 20, 2023 | Apr 20, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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All patients will be randomly divided into two groups, each will receive a different luteal treatment:
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| Drug |
dose as mentioned |
|
| Progesterone 100Mg Vag Tab | Drug | dose as mentioned |
|
| up to two month after embryo transfer |
| Ectopic pregnancy rate | number of ectopic pregnancy divided by number of positive beta-hCG | up to two month after embryo transfer |
| Miscarriage rate | number of non-viable before 24 weeks divided by total number of positive beta-hCG | up to 20 weeks after embryo transfer |
| Live birth rate | number of live births after 24 weeks divided by number of transfers. | up to 42 weeks after embryo transfer |
| 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. |
| 17980870 | Background | 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. |
| 21840758 | Background | 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. |
| 32395750 | Background | 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. |
| 28675921 | Background | 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. |
| 27798046 | Background | 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. |
| 20097333 | Background | 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. |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D045167 | Progesterone Congeners |
| D012739 | Gonadal Steroid Hormones |