Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

STUDY QUESTION: Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER: Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY: The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION: Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE: Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION: This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT01786252). TRIAL REGISTRATION DATE: 5 February 2013. DATE OF FIRST PATIENT'S ENROLLMENT: 10 May 2013.

Favorable pregnancy, delivery, and implantation rates experienced in embryo donation programs in the United States.

OBJECTIVE: To document the numbers of donated frozen ETs performed and the pregnancy, birth, and embryo implantation rates seen in four infertility clinics and three embryo donation agencies in the United States. DESIGN AND SETTING: Case series. Four infertility clinics and three embryo donation agencies in the United States contributed data from their first year of available information through calendar year 2006. The programs reported numbers of donated frozen ETs, numbers of pregnancies delivered from these transfers, and numbers of these pregnancies lost to miscarriage or stillbirth. For each pregnancy, the programs reported the number of gestational sacs identified and the number of resulting live births. PATIENT(S): N/A. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Pregnancy rate, delivery rate per ET, implantation rate, live birth rate per embryo transferred, and "implantation potential" (gestational sacs identified per embryo thawed). RESULT(S): These programs performed 702 ETs, resulting in 314 clinical pregnancies (44.7%) and 249 deliveries (35.5%). With 3,103 embryos thawed and 2,078 embryos transferred, the programs experienced an implantation rate of 19.9%, an implantation potential of 11.8%, and a live birth rate per embryo transferred of 15.0%. CONCLUSION(S): In this largest case series yet published, the pregnancy, delivery, and implantation rates for embryo donation compare favorably with rates reported from autologous IVF procedures.

The integration of psychiatric rehabilitation services in behavioral health care structures: a state example.

This article describes a model for integrating psychiatric rehabilitation services in a managed behavioral health care structure. Psychiatric rehabilitation and managed care are two distinct developments in the provision of mental health services that have proceeded independently though they can have compatible methods and outcomes. Descriptive detail is provided about a state initiative in Iowa to provide psychiatric rehabilitation services to those with serious mental illness through the state-contracted managed behavioral health care corporation. The article describes factors leading to the program's implementation, service delivery structures, reimbursements, personnel requirements, and performance indicators. Evidence for supporting this innovation is provided through a case-controlled outcomes study of mental health service units used and their costs for participants and matched controls.