Exogenous gonadotropins for poor endometrial responders

Exogenous gonadotropins for poor endometrial responders

an influential role in female reproductive physiology and diseases involved in tissue implant and angiogenesis. Supported by: This project was Support...

52KB Sizes 0 Downloads 46 Views

an influential role in female reproductive physiology and diseases involved in tissue implant and angiogenesis. Supported by: This project was Supported by the Jones Foundation for Reproductive Medicine.

P-478 Wednesday, October 22, 2014 EXOGENOUS GONADOTROPINS FOR POOR ENDOMETRIAL RESPONDERS. J. M. Cox,a M. J. Hill,a K. Devine,a K. S. Richter,b A. DeCherney,a M. Levy.b aPRAE, NICHD, NIH, Bethesda, MD; bShady Grove Fertility, Rockville, MD. OBJECTIVE: Frozen embryo transfer (FET) and donor oocyte recipient cycles (DRC) typically employ exogenous estrogen to prepare the endometrium. At ultrasound assessment, many patients have an endometrium considered too thin or of an inadequate pattern to expect typical pregnancy. Our objective was to evaluate the effect of gonadotropin stimulation on endometrial development in patients with history of poor endometrial development undergoing FET or donor cycles. DESIGN: Retrospective analysis. FET or DRC utilizing gonadotropins for endometrial development were compared to their own prior cycles treated with exogenous estrogen without gonadotropins. MATERIALS AND METHODS: Women who underwent at least one FET or DRC with gonadotropin stimulation for endometrial preparation were identified from 2004-2012. Generalize estimating equations (GEE) were used to compare both continuous and dichotomous variables. This modeling accounted for nesting of multiple cycles contributed by one patient both for control and treatment cycle groups. RESULTS: 39 patients were included, totaling 63 treatment cycles utilizing gonadotropins and 105 control cycles. Control cycles had higher peak estradiol. Despite this, the treatment group had higher peak endometrial thickness (EMT), lower odds of cycle cancellation for poor endometrial development, and higher odds of live birth (Table 1). In GEE modeling, gonadotropin treatment had higher odds of live birth (OR 1.30, 95%CI 1.13-1.49).

Table 1

Outcome

Control Gonadotropin Cycles Cycles (n¼105) (n¼63)

Peak Estradiol 2333 Mean Endometrial 7.1  1.8 Thickness % Cancelled (poor 43.8 endometrium) % Live Birth 6.7

OR (95%CI)

P value

930 8.3  2.7

-1403 (1036-1770) <0.01 1.2 (0.15-2.2) <0.001

17.4

0.76 (0.65-0.89) <0.001

33.3

1.31 (1.14-1.50) <0.001

CONCLUSION: This retrospective analysis suggests that some patients who have poor endometrial development from exogenous estrogen alone may benefit from exogenous gonadotropins in FET and DRC. This effect was not associated with estradiol concentration, suggesting potential benefit of endogenous estrogen or gonadotropin effect. The study design has potential bias due to regression to the mean, however, these data suggest this treatment should be evaluated in a prospective controlled fashion. Supported by: In part by PRAE, NICHD, NIH.

P-479 Wednesday, October 22, 2014 HIGH FSH LEVEL INCREASE ENDOMETRIAL ATROPHY THROUGH CROSS-TALK WITH TGF BETA SIGNAL TRANSDUCTION PATHWAY IN POST-MENOPAUSE WOMEN. J. Li,a,b D. Zhang,a,b G. Xu,a,b L. Chen,a,b Y. Qian,a Y. Liu,a,b C. Zhou,a H. Huang.a,b,c aKey Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, Zhejiang, China; bDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; cInternational Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai, China.

e296

ASRM Abstracts

OBJECTIVE: Investigate whether high serum follicle-stimulating hormone (FSH) in post-menopause women might promote endometrial atrophy by crosstalk with TGF beta signal transduction pathway. DESIGN: Observe effects of FSH on post-OVX endometrial atrophy in mice and effects of FSH on proliferation and apoptosis in human primary cultured endometrial cell. MATERIALS AND METHODS: Endometrium was obtained from childbearing age women for primary culture. After digestion, endometrial cell were cultured in medium with 0, 50,100,150 IU/L FSH for 72hrs. Proliferation was measured via BrdU assay and markers for apoptosis and proliferation were measured via western-blot. Endometrial cell were cultured in medium with 100 IU/L FSH for 0, 30, 60,120mins. Activation of TGF beta signal transduction pathway was measured by western-blot. We made four mouse models: SHAM, OVX, OVX+GnRH, OVX+GnRH+FSH. Serum levels of FSH and estradiol were measured. The weight and morphology of uterus from those animal models were analyzed. RESULTS: [1] FSH receptor was expressed in human endometrial cell using western blot, RT-PCR and IF. Its expression levels did not varied significantly in pre- and peri-menopausal women. [2] FSH inhibited the proliferation and promoted the apoptosis of primary cultured endometrial cell in a dose-dependent way, which reached a peak at 100IU/L (P<0.05). Up-regulation of cell apoptosis markers (caspase3, caspase8 and caspase9) and down-regulation of proliferation relative gene c-Jun were also shown. [3] FSH can promote the phosphorylation and nucleus translocation of Smad2/Smad3 in a time-dependent way which reached a plateau at 60mins (p<0.05) which can be partly reversed by pretreatment with antibody against TGF beta receptor II (TbRII, 100ng/ml). [4]Serum FSH of OVX and OVX+GnRH+FSH groups were higher than SHAM and OVX+GnRH groups(P<0.01). In groups with high FSH, more significant changes involved with apoptosis after OVX were observed. Those changes include the smaller size of glandular tube, the pyknotic nuclei, the vacuolization in mitochondria and the hollowed rough endoplasmic reticulum. CONCLUSION: High FSH in post-menopause women inhibited proliferation of endometrial adenocyte by cross-talking with TGF beta signaling, which promoted endometrial atrophy. Supported by: the National Basic Research Program of China (No. 2013CB967404), the National Natural Science Foundation of China (No.81270664, 81170310), the Public Welfare Technology Application Research Project of Zhejiang Province (No.2010C33167), the Talent Project of Zhejiang Province (No.2011RCA028), and the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT1184).

P-480 Wednesday, October 22, 2014 INTRA-MUSCULAR LONG ACTING GNRH AGONIST(DECAPEPTYLEÒCR,TRIPTORELIN 3.75)INJECTION ON THE FIRST DAY OF THE MENSTRAL CYCLE INCREASES THE THICKNESS OF RESISTING THIN ENDOMETRIUM. H. Sahebkashaf, S. Sahebkashaf, Z. Shalchian, A. Sahebkashaf, M. Ashoori, M. Sahebkashaf. Center for Reproductive Medicine and Surgery, Navid, Infertility Institute, Tehran, Islamic Republic of Iran. OBJECTIVE: To evaluate the flare-up effect of an intra-muscular injection of long-acting GnRH agonist on the first day of the menstrual cycle to increase the thickness of resisting thin endometrium and improve pregnancy outcome. DESIGN: Prospective Cohort, Proof of concept study. MATERIALS AND METHODS: This prospective cohort study was conducted in a large private art center in 510 infertile patients with successive implantation failures and resisting thin endometrium. Being recipients of fresh donor or frozen embryos from Jan 2004-2014. Long-acting GnRH agonist was injected on the first day of the cycle also oral Conjugated estrogens USP(EQIN-ActoverCo) was started at 1.25mg and increased to a maximum daily dose of 3.75 mg. Endometrial thickness was controlled with ultrasound and progesterone was initiated . RESULTS: Mean endometrial thickness was increased from 5.3 mm to 6.1 mm (p¼ 0.007). 36% of the patients had more than 25% improvement of their endometrial thickness. 18% achieved an endometrial thickness above 7mm and in 18% endometrial thickness did not improved at all. overall The live birth rate was 39% (198/510). CONCLUSION: To our knowledge this is the first study to investigate the possible consequences of a flare-up of intra-muscular injection of long acting GnRH agonist on the first day of the menstrual cycle to increase

Vol. 102, No. 3, Supplement, September 2014