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The investigators attempted to compare the clinical outcomes and cumulus genes expression in poor ovarian responders undergoing luteal ovarian stimulation or follicular ovarian stimulation in in vitro fertilization cycles.
Multiple follicular wave theory proposed by Baerwald et al. implied that follicle recruitment may occur in the luteal phase of menstrual cycle. Therefore, luteal phase ovarian stimulation (LPOS) was considered as a potential feasible stimulation method during in vitro fertilization (IVF) cycle. In the beginning, in order to avoid delaying cancer treatment, LPOS was applied for fertility preservation of cancer patients, showing no difference in numbers of oocyte retrieved, mature oocytes and fertilization rate between luteal or follicular phase stimulation. In the recent, LPOS was used for infertility women, suggesting that LPOS owned quite good IVF outcomes. In previous studies, premature luteinizing hormone (LH) surge, a major reason worsening ovarian quality in poor ovarian responders (PORs), was seldom found in LPOS. High progesterone in luteal phase may aid in suppressing premature LH surge. An updated research claimed that numbers of oocyte retrieved, mature oocytes and fertilized oocytes in LPOS significantly increased when compared to follicular ovarian stimulation. Therefore, the investigators presumed that LPOS was a more effective method than follicular stimulation in PORs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| luteal ovarian stimulation | Experimental | The controlled ovarian stimulation in in vitro fertilization cycle was started since luteal phase. |
|
| follicular ovarian stimulation | Active Comparator | The controlled ovarian stimulation in in vitro fertilization cycle was started since early follicular phase phase. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| luteal ovarian stimulation | Other | In the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase. |
|
| Measure | Description | Time Frame |
|---|---|---|
| oocytes and embryos | retrieved oocytes in number, matured oocytes in number, fertilized oocytes in number, day 3 embryos in number, top-quality day 3 embryos in number | through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| pregnancy rate | Clinical pregnancy rate | Pregnancy will be confirmed 4 weeks after embryo transfer. |
| genes expression | cumulus cells genes expression |
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Inclusion Criteria:
Poor ovarian responders (PORs) met the Bologna criteria, having at least two of the three following features:
Moreover, two episodes of a previous POR after maximal stimulation alone would be sufficient to define a patient as a POR.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kuan-Hao Tsui, PhD | Kaohsiung Veterans General Hospital. | Study Director |
| Salvatore Giovanni Vitale, M.D. | University of Messina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kaohsiung Veterans General Hospital | Kaohsiung City | 81362 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12849812 | Background | Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2. | |
| 22068695 | Background | Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8. |
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| follicular ovarian stimulation | Other | In the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase. |
|
| through study completion, an average of 1 year |
| 20455017 | Result | Bedoschi GM, de Albuquerque FO, Ferriani RA, Navarro PA. Ovarian stimulation during the luteal phase for fertility preservation of cancer patients: case reports and review of the literature. J Assist Reprod Genet. 2010 Aug;27(8):491-4. doi: 10.1007/s10815-010-9429-0. Epub 2010 May 9. |
| 18930226 | Result | von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, Strowitzki T. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009 Oct;92(4):1360-1365. doi: 10.1016/j.fertnstert.2008.08.011. Epub 2008 Oct 18. |
| 20688325 | Result | Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011 Jan;95(1):64-7. doi: 10.1016/j.fertnstert.2010.06.064. Epub 2010 Aug 5. |
| 23635348 | Result | Cakmak H, Rosen MP. Ovarian stimulation in cancer patients. Fertil Steril. 2013 May;99(6):1476-84. doi: 10.1016/j.fertnstert.2013.03.029. |
| 23987516 | Result | Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013 Dec;100(6):1673-80. doi: 10.1016/j.fertnstert.2013.07.1992. Epub 2013 Aug 26. |
| 24161646 | Result | Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23. |
| 25154677 | Result | Martinez F, Clua E, Devesa M, Rodriguez I, Arroyo G, Gonzalez C, Sole M, Tur R, Coroleu B, Barri PN. Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes. Fertil Steril. 2014 Nov;102(5):1307-11. doi: 10.1016/j.fertnstert.2014.07.741. Epub 2014 Aug 22. |
| 25444501 | Result | Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6. |
| 26370530 | Result | Li Y, Yang W, Chen X, Li L, Zhang Q, Yang D. Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response. Gynecol Endocrinol. 2016;32(1):74-7. doi: 10.3109/09513590.2015.1081683. Epub 2015 Sep 15. |
| 26927248 | Result | Wei LH, Ma WH, Tang N, Wei JH. Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol: A retrospective study. Taiwan J Obstet Gynecol. 2016 Feb;55(1):50-4. doi: 10.1016/j.tjog.2015.07.001. |
| 33746576 | Derived | Chen YC, Li JY, Li CJ, Tsui KH, Wang PH, Wen ZH, Lin LT. Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study. Int J Med Sci. 2021 Feb 4;18(7):1600-1608. doi: 10.7150/ijms.55955. eCollection 2021. |
| 29869107 | Derived | Lin LT, Vitale SG, Chen SN, Wen ZH, Tsai HW, Chern CU, Tsui KH. Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study. Adv Ther. 2018 Jun;35(6):847-856. doi: 10.1007/s12325-018-0713-1. Epub 2018 Jun 4. |