We undertook this retrospective variables-control analysis to compare the reproductive outcomes of frozen-thawed embryo transfer using endometrial preparation with either natural cycle or hormone replacement therapy cycle. Patients were divided into three subgroups. Subgroup A (n = 32) consisted of patients having three 8-cell post-thawed embryos transferred. Subgroup B (n = 404) consisted of patients having three good quality post-thawed embryos transferred. Subgroup C (n = 578) consisted of patients having two or three all intact and mitosis resumption post-thawed embryos transferred. Implantation rate, biochemical pregnancy rate, and clinical pregnancy rate were measured. In subgroup A, significantly higher implantation rate, clinical pregnancy rate ongoing pregnancy rate, and lower biochemical pregnancy rate were observed in the natural cycle compared with hormone replacement therapy (HRT) cycle. Subgroup B, had a significantly higher rate of implantation, ongoing pregnancy, and a significantly lower rate of biochemical pregnancy in natural cycle compared with HRT cycle. The natural cycle had a higher trend of clinical pregnancy rate without reaching statistical significance. No statistical difference in reproductive outcomes between natural cycle and HRT cycle was observed in subgroup C. The results suggest the superiority of the natural cycle as compared with the HRT cycle under certain circumstances in a selected population of patients.

Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are induced by in vivo and in vitro decidualization. OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion.

Embryo implantation is a highly synchronized bioprocess between an activated blastocyst and a receptive uterus. In mice, successful implantation relies on the dynamic interplay of estrogen and progesterone; however, the key mediators downstream of these hormones that act on blastocyst competency and endometrium receptivity acquisition are largely unknown. In this study, we showed that the expression of osteopontin (OPN) in mouse blastocysts is regulated by ovarian estrogen and uterine micro-environment. OPN mRNA is up-regulated in mouse blastocyst on day 4 of pregnancy, which is associated with ovarian estrogen secretion peak. Hormone treatment in vivo demonstrated that OPN expression in a blastocyst is regulated by estrogen through an estrogen receptor (ER). Our results of the delayed and activated implantation model showed that OPN expression is induced after estrogen injection. While estrogen treatment during embryo culture in vitro showed less effect on OPN expression, the tubal ligation model on day 3 of pregnancy confirmed that the regulation of estrogen on OPN expression in blastocyst might, through some specific cytokines, have existed in a uterine micro-environment. Collectively, our study presents that estrogen regulates OPN expression and it may play an important role during embryo implantation by activating blastocyst competence and facilitating the endometrium acceptable for active blastocyst.

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group), and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH), antral follicle count (AFC), duration and total dosage of gonadotropin (Gn), number of oocytes retrieved, intracytoplasmic sperm injection (ICSI) rate, fertilization rate, and cycle cancellation rate between the two groups (P>0.05). However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P<0.05). By the end of April 2017,62 FET cycles were conducted in PPOS group. The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%, respectively. In conclusion, PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ICSI-ET cycles.

Objective This study aimed to compare the pregnancy outcomes between women receiving frozen embryo transfer (FET) with hormone replacement treatment (HRT) with and without gonadotropin-releasing hormone agonist (GnRHa) pretreatment. Methods All consecutive women undergoing HRT cycles (2936 cycles) or HRT with GnRHa pretreatment (HRT + GnRHa, 303 cycles) at our reproductive center between January 2015 and December 2017 were analyzed retrospectively. Results The average age was higher in the HRT + GnRHa compared with the HRT group (34.0 ± 4.8 vs. 31.3 ± 4.4). However, the pregnancy outcomes were comparable between the two groups. The clinical pregnancy rate was significantly increased in younger women (≤35 years) in the HRT + GnRHa group compared with the HRT group (56.8% vs. 48.7%), but the live birth rates were similar in the two groups (44.2% vs. 38.4%). The HRT + GnRHa protocol significantly increased the clinical pregnancy rate (55.6% vs. 43.2%) and live birth rate (43.5% vs. 33.5%) compared with the HRT group among women with endometriosis, and significantly decreased the abortion rate in women with polycystic ovarian syndrome (3.1% vs. 16.4%). Conclusions GnRHa pretreatment may improve pregnancy outcomes in women with endometriosis and polycystic ovarian syndrome.