Implantation Rate and Clinical Pregnancy Rate According to Dosage and Timing of Progesterone Administration for Secretory Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles

동결보존 배아이식에서 분비기 자궁내막 유도시 프로게스테론 투여 방법에 따른 착상율과 임신율의 비교

  • Park, Chan-Woo (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Hur, Kuol (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Moon-Young (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Song, Hyun-Jung (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hye-Ok (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Yang, Kwang-Moon (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jin-Yeong (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Song, In-Ok (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Yoo, Keun-Jae (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Cheon, Kang-Woo (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Byun, Hye-Kyung (Laboratory of Reproductive Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Koong, Mi-Kyoung (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine) ;
  • Kang, Inn-Soo (Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine)
  • 박찬우 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 허걸 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 김문영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 송현정 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 김혜옥 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 양광문 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 김진영 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 송인옥 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 유근재 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 천강우 (성균관대학교 의과대학 삼성제일병원 생식내분비 및 불임 연구실) ;
  • 변혜경 (성균관대학교 의과대학 삼성제일병원 생식내분비 및 불임 연구실) ;
  • 궁미경 (성균관대학교 의과대학 삼성제일병원 산부인과) ;
  • 강인수 (성균관대학교 의과대학 삼성제일병원 산부인과)
  • Published : 2003.09.30

Abstract

Objective: To evaluate the difference of implantation rate (IR) and clinical pregnancy rate (CPR) between two protocols of endometrial preperation in women undergoing frozen-thawed embryo transfer (FET) cycles. Methods: This study was performed during the different time periods: A retrospective study from January 2000 to June 2001 (phase I) and a prospective study from July 2001 to March 2002 (phase II). All the patients received estradiol valerate (6 mg p.o. daily) starting from day 1 or 2 of the menstrual cycle without pituitary down regulation. Progesterone was administered around day 14 after sonographic confirmation of endometrial thickness $\geq$7 mm and no growing follicle. In Group A (n=88, 99 cycles) of phase I, progesterone was administered i.m. at a dose of 50 mg daily from one day prior to thawing of pronuclear (PN) stage frozen embryo or three days prior to thawing of 6-8 cell stage frozen embryo and then each stage embryos were trasnsferred 2 days or 1 day later after thawing. In Group B (n=246, 299 cycles) of phase I, patients recieved progesterone 100 mg i.m. from one day earlier than group A; two days prior to PN embryo thawing, four days prior to of 6-8 cell embryo thawing. During the phase II, to exclude any differences in embryo transfer procedures, in Group 1 (n=23, 28 cycles) of phase II embryo was transfered by one who have used the progesterone protocol since the phase I. In Group 2 (n=122, 139 cycles) of phase II embryo was transfered by one who use the progesterone protocol from the phase II. Results: When compared across the phase and group, there were no significant differences in the characteristics. During the phase I, there were significant increase in IR (14.4% vs 5.9%, p=0.001) and CPR (28.3% vs 14.5%, p=0.000) in group A. During the phases II, IR (11.8% vs 10.6%) and CPR (27.6% vs 27.3%) show no differences between two groups. Conclusions: In FET cycles, IR and CPR are increased significantly by the change of dosage and timing of progesterone administraton. And the timing is considered to be more important factor because the dosage of progesterone did not affect implantation window in previous studies. Therefore, we suggest that progesterone administration in FET cycle should begin from one day prior to PN stage embryo thawing and three days prior to 6-8 cell stage embryo thawing.

Keywords

References

  1. Elder K, Dale B. In vitro fertilization. In: Cryopreservation. 2nd ed. Cambridge University Press; 2002. p.192-227
  2. Pattinson AH, Greene CA, Fleetham J, Anderson-Sykes SJ. Exogenous control of the cycle simplifies thawed embryo transfer and results in pregnancy rate similar to that of natural cycles. Fertil Steril 1992; 58: 627-9 https://doi.org/10.1016/S0015-0282(16)55278-9
  3. Society for Assisted Reproductive Technology American Society for Reproductive Medicine. Assisted reproductive technology in the United States and Canada: 1994 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 1996; 66: 697-705
  4. Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril 1994; 62: 485-90 https://doi.org/10.1016/S0015-0282(16)56935-0
  5. Rosenwaks Z, Veeck LL, Liu HC. Pregnancy following transfer of in vitro fertilized donated oocytes. Fertil Steril 1986; 45: 417-20 https://doi.org/10.1016/S0015-0282(16)49228-9
  6. Sathanandan M, Macnamee MC, Rainsbury P, Wick K, Brinsden P, Edwards RG. Replacement of frozenthawed embryos in artificial and natural cycles: a prospective semi-randomized study. Hum Reprod 1991; 6: 685-7 https://doi.org/10.1093/oxfordjournals.humrep.a137407
  7. Cohen J, Decane GW, Elsner CW, Kort HI, Massey JB, Norbury SE. Cryopreserved zygotes and embryos and endocrinologic factors in the replacement cycle. Fertil Steril 1988; 50: 61-7 https://doi.org/10.1016/S0015-0282(16)60009-2
  8. Testart J, Lasslle B, Belaisch-Allart J, Forman R, Hazout A, Fries N, Frydman R. Human embryo freezing. Ann N Y Acad Sci 1988; 541: 532-40 https://doi.org/10.1111/j.1749-6632.1988.tb22289.x
  9. Muasher SJ, Kruithoff C, Simonetti S, Oehninger S, Acosta AA, Jones GS. Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycle. Hum Reprod 1991; 6: 443-5 https://doi.org/10.1093/oxfordjournals.humrep.a137355
  10. Serhal PF, Craft IL. Ovum donation - a simplified approach. Fertil Steril 1987; 48:265-9 https://doi.org/10.1016/S0015-0282(16)59354-6
  11. Schmidt CL, de Ziegler D, Galiardi CL, Mellon RW, Taney FH, Kuhar MJ, Colon JM, Weiss G. Transfer of cryopreserved-thawed embryo: the natural cycle versus controlled preparation of the endometrium with gonadotropin-releasing hormone agonist and exogenous estradiol and progesterone (GEEP). Fertil Steril 1989; 52: 609-16 https://doi.org/10.1016/S0015-0282(16)60973-1
  12. Muasher SJ, Kruithoff C, Simonetti S, Oehninger S, Acosta AA, Jones GS. Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycle. Hum Reprod 1991;6: 443-5 https://doi.org/10.1093/oxfordjournals.humrep.a137355
  13. Al-Shawaf T, Yang D, Al-Magid Y, Seaton A, Iketubosin F, Craft I. Ultrasonic monitoring during replacement of frozen/thawed embryo in natural and hormone replacement cycle. Hum Reprod 1993; 8: 2067-70
  14. Queenan J, Veeck LL, Seltman H, Muasher S. Transfer of cryopreserved thawed pre-embryos in a natual cycle or a programmed cycle with exogenous hormonal replacement yields similar pregnancy results. Fertil Steril 1994; 62: 545-50 https://doi.org/10.1016/S0015-0282(16)56943-X
  15. Younis JS, Mordel N, Lewin A. Artificial endometrial preperation for oocyte donation: the effect of estrogen stimulation on clinical outcome. J Assist Reprod Genet 1992; 9: 222-7 https://doi.org/10.1007/BF01203817
  16. Remohi J, Vidal A, Pellicer A. Oocyte donation in low reponders to conventional ovarian stimulation for in vitro fertilization. Fertil Steril 1993; 59: 1208-15 https://doi.org/10.1016/S0015-0282(16)55978-0
  17. Nezhat C, Kapas AE, Greenblatt RB, Mahesh VB. Estradiol implants for conception control. Am J Obstet Gynecol 1980; 138: 1151-6 https://doi.org/10.1016/S0002-9378(16)32783-1
  18. Godman RL, Bittman EL, Foster DL, Karsch FJ. The endocrine basis of the synergistic suppression of luteinizing hormone by estradiol and progesterone. Endocrinology 1981; 109: 1414-7 https://doi.org/10.1210/endo-109-5-1414
  19. Yaron Y, Amit A, Mani A, Yovel I, Kogosowski A, Peyser MR, David MP, Lessing JB. Uterine preparation with estrogen for oocyte donation: assessing the effect of treatment duration on pregnancy rates. Fertil Steril 1995; 63: 1284-6 https://doi.org/10.1016/S0015-0282(16)57612-2
  20. Queenan JT Jr, Ramey JW, Seltman HJ, Eure L, Veeck LL, Muasher SJ. Transfer of cryopresevedthawed pre-embryos in cycle using exogenous steroids without prior gonadotrophin-releasing hormone agonist suppression yields favourable pregnancy results. Hum Reprod 1997; 12: 1176-80 https://doi.org/10.1093/humrep/12.6.1176
  21. Navot D, Laufer N, Koplovic J, Rabinowitz R, Birkenfeld A, Lewin A, Granat M, Margalioth EJ, Schenker JG. Artificially induced endometrial cycles and establishment of pregnancies in the absence of the ovaries. N Engl J Med 1986; 314: 806-11 https://doi.org/10.1056/NEJM198603273141302
  22. Rosenwaks Z, Veeck LL, Liu HC. Pregnancy following transfer of in vitro fertilized donated oocytes. Fertil Steril 1986; 45: 417-20 https://doi.org/10.1016/S0015-0282(16)49228-9
  23. Serhal PF, Craft IL. Ovum donation-a simplified approach. Fertil Steril 1987; 48: 265-9 https://doi.org/10.1016/S0015-0282(16)59354-6
  24. Asch R, Balmaceda J, Ord T. Oocyte donation and gamate intrafallopian transfer as treatment for premature ovarian failure. Lancet 1987; I: 687-8
  25. Navot D, Scott RT, Droesch K, Veek LL, Liu HC, Rosenwaks Z. The window of embryo transfer and the effuciency of human conception in vitro. Fertil Steril 1991; 55: 114-8 https://doi.org/10.1016/S0015-0282(16)54069-2
  26. Prapas Y, Prapas N, Jones EE. The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy. Hum Rerod 1998; 13: 1720-3
  27. Rosenwaks Z. Donor eggs:their application in morden reproductive technologies. Fertil Steril 1987; 47: 895-909 https://doi.org/10.1016/S0015-0282(16)59220-6
  28. Graf MJ, Reyniak JV, Battle-Mutter P, Laufer N. Histologic evaluation of the luteal phase in women following folicle aspiration for oocyte retrieval. Fertil Steril 1988; 49: 616-9 https://doi.org/10.1016/S0015-0282(16)59828-8
  29. Ben-Nun I, Siegal A, Ghetler Y, Kneti H, Jaffe R, Fejgin R. Effect of preovulatory progesterone administration on the endometrial maturation and implantation rate after in vitro fertilization and embryo transfer. Fertil Steril 1990; 53: 276-81 https://doi.org/10.1016/S0015-0282(16)53281-6