Extended hypo-estrogenic treatment might enhance implantation in those who have failed to conceive after multiple embryo transfers

Abstract

OBJECTIVE: It is well known that the pregnancy rate (PR) is higher in recipient women without ovarian function than those with ovarian function in oocyte donation programs, though the mechanism is not clear. We investigated whether extended hypo-estrogenic state with GnRHa treatment might be effective to enhance implantation in those who have failed to conceive after multiple embryo transfers.DESIGN: A prospective clinical study was carried out at a private IVF clinic between October 2006 and December 2007.MATERIALS AND METHODS: A total of 98 women, who had failed to conceive after three or more fresh and frozen thawed ETs (FET), entered this study. Thirty-three women who agreed to have this treatment were given GnRH agonist (Leuplin 1.88mg, Takeda, Japan) once a month for 1 to 3 months to induce at least one month duration of hypo-estrogenic state prior to FET. Sixty-five women who had FET during the same period were served as the control group and received OC for a month prior to FET. Endometrium was prepared with oral and patched estrogen (E) and progesterone (P) IM in all FET cycles. Only blastocysts were vitrified with cryoloop and transferred on the 5th day after P administration. Serum HCG was measured on the 14th day after P administration and pregnancy was determined with the presence of fetal heart beat.RESULTS: Thirty-three FET cycles were performed in the study group and 78 cycles were performed in control. Mean age of women was 36.9 in study group and 36.1 in control. The number of previous ET cycles was 4.1(3-6) and 4.1 (3-8), respectively. The number of patients with diagnosis of endometriosis and/or myoma was 5 and 9, respectively and there were no differences in their proportion of the groups. The mean number of blastocysts transferred was 1.4 in both groups and their grades at the time of vitrification were similar according to blastocyst grading score. The implantation rate and ongoing PR were 42.6% (20/47) and 51.5% (17/33) in study group, and 26.1% (29/111) and 28.2% (22/78) in control group, respectively. These differences were statistically significant (p<0.05).CONCLUSIONS: Although the mechanism is not clear, extended hypo-estrogeninc treatment with GnRH agonist may affect the sensitivity of E and P and/or enzyme expression, such as aromatase cytochrome p450 in endometrium and resulted in an increased implantation rate in those who had a history of multiple implantation failures. OBJECTIVE: It is well known that the pregnancy rate (PR) is higher in recipient women without ovarian function than those with ovarian function in oocyte donation programs, though the mechanism is not clear. We investigated whether extended hypo-estrogenic state with GnRHa treatment might be effective to enhance implantation in those who have failed to conceive after multiple embryo transfers. DESIGN: A prospective clinical study was carried out at a private IVF clinic between October 2006 and December 2007. MATERIALS AND METHODS: A total of 98 women, who had failed to conceive after three or more fresh and frozen thawed ETs (FET), entered this study. Thirty-three women who agreed to have this treatment were given GnRH agonist (Leuplin 1.88mg, Takeda, Japan) once a month for 1 to 3 months to induce at least one month duration of hypo-estrogenic state prior to FET. Sixty-five women who had FET during the same period were served as the control group and received OC for a month prior to FET. Endometrium was prepared with oral and patched estrogen (E) and progesterone (P) IM in all FET cycles. Only blastocysts were vitrified with cryoloop and transferred on the 5th day after P administration. Serum HCG was measured on the 14th day after P administration and pregnancy was determined with the presence of fetal heart beat. RESULTS: Thirty-three FET cycles were performed in the study group and 78 cycles were performed in control. Mean age of women was 36.9 in study group and 36.1 in control. The number of previous ET cycles was 4.1(3-6) and 4.1 (3-8), respectively. The number of patients with diagnosis of endometriosis and/or myoma was 5 and 9, respectively and there were no differences in their proportion of the groups. The mean number of blastocysts transferred was 1.4 in both groups and their grades at the time of vitrification were similar according to blastocyst grading score. The implantation rate and ongoing PR were 42.6% (20/47) and 51.5% (17/33) in study group, and 26.1% (29/111) and 28.2% (22/78) in control group, respectively. These differences were statistically significant (p<0.05). CONCLUSIONS: Although the mechanism is not clear, extended hypo-estrogeninc treatment with GnRH agonist may affect the sensitivity of E and P and/or enzyme expression, such as aromatase cytochrome p450 in endometrium and resulted in an increased implantation rate in those who had a history of multiple implantation failures.