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Papers by Ai Ai

$Research paper thumbnail of The M2 polarization of macrophage induced by fractalkine in the endometriotic milieu enhances invasiveness of endometrial stromal cells$

Fractalkine (FKN) is involved in the immunopathogenesis of inflammatory diseases, including endom... more Fractalkine (FKN) is involved in the immunopathogenesis of inflammatory diseases, including endometrio - sis. Our objective was to investigate the role of FKN in the cross-talking between endometrial stromal cells (ESCs) and U937 (macrophage line) in the endometriotic milieu. We have found that FKN levels in peritoneal fluid and ESCs positively correlate with the progress of endometriosis. The expression of CX3CR1 in the normal ESCs were signifi - cantly lower than that in eutopic and ectopic ESCs from women with endometriosis. CX3CR1 expression in U937 was higher than that in ectopic ESCs. FKN secreted by eutopic ESCs could change the balance between the release of IL10 and IL12 of macrophages with the upregulation of IL10 production and downregulation of IL12 produc- tion. Moreover, FKN could induce M2 polarization of macrophage with decreased expression of CD86. FKN could increase the expression of matrix metalloproteinase 9 and decrease the expression of tissue inhibitor of meta...

American Journal of Medical Case Reports, 2017

This study reports an IVF patient who had adenomyosis underwent 2 in vitro fertilization (IVF) cy... more This study reports an IVF patient who had adenomyosis underwent 2 in vitro fertilization (IVF) cycles and 3 frozen embryo transfer (FET) cycles but all failed. Then a Levonorgestrel-releasing intrauterine system (LNG-IUS) was inserted into her uterine. When her next menstrual period did not occur, the patient performed a urinary pregnancy test and it was positive. The pregnancy progressed normally and the delivery was uncomplicated. An elective Caesarean delivery was performed at 39 weeks gestation. The IUD was found in the placenta and the postpartum recovery was uneventful. This is the first report of a woman, who having been identified with uterine adenomyosis, delivered a normal female infant with an LNG-IUS in situ. This case report indicated that LNG-IUS may play some roles in changing the uterine environment of adenomyosis.

Different endometrial preparation protocols yield similar pregnancy outcomes for frozen-thawed embryo transfer in patients with advanced endometriosis

Journal of Reproduction and Contraception, 2016

Objective To explore the different endometrial preparation for frozen-thawed embryo transfer (FET... more Objective To explore the different endometrial preparation for frozen-thawed embryo transfer (FET) in women with advanced endometriosis (EMS). Methods The pregnancy outcomes of patients with advanced EMS (542 cycles), who were prepared for FET, were retrospectively assessed. Included patients underwent a total of 233 FET cycles (180 patients) using natural cycle (NC), a total of 142 FET cycles (115 patients) using letrozole (LE) ovulation induction, and a total of 167 FET cycles (137 patients) using hormonal replacement treatment (HRT) for endometrial preparation. Results There were no significant diffenences in the clinical pregnancy rate (LE: 49.30%, NC: 50.21%, and HRT: 43.11%, P=0.343), the implantation rate (LE: 29.26%, NC: 36.03%, and HRT: 29.55%, P=0.084), and the live birth rate (LE: 38.02%, NC: 39.11%, and HRT: 35.33%, P=0.648) among the three groups. No statistically significant differences were observed in the ongoing pregnancy rate, the miscarriage rate, and the pregnanc...

Background: Time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessment s... more Background: Time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessment system. Compared with conventional incubators, it provides stable culture condition and consistent observation of embryo development, thereby improving embryo quality and selection. In theory, these benefits could improve clinical outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Although this system has been routinely used in many IVF centers globally, it remains unclear if the TLS results in higher cumulative live birth rate and high-quality evidence is warranted. The purpose of this study is to compare the effectiveness of the TLS with conventional incubators in infertile diminished ovarian reserve (DOR) patients. Methods: This study is a double-blind randomized controlled clinical trial (1:1 treatment ratio of TLS vs. conventional incubator). A total of 730 DOR patients undergoing the first or second cycle of IVF or ICSI will be enrolled and randomiz...

BMJ Open, 2020

IntroductionThe time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessme... more IntroductionThe time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessment system. Compared with conventional incubators, a TLS provides stable culture conditions and consistent observations of embryo development, thereby potentially improving embryo quality and selection of the best quality embryo. Although TLSs have been routinely used in many in vitro fertilisation (IVF) centres globally, there is insufficient evidence to indicate that TLSs result in higher cumulative live birth rates over conventional incubators. The purpose of this study is to compare the cumulative live birth rates and safety including miscarriage in infertile patients with diminished ovarian reserve (DOR) from both TLSs and conventional incubators.Methods and analysisThis study is a double-blind randomised controlled clinical trial (1:1 treatment ratio of TLSs vs conventional incubator). A total of 730 patients with DOR undergoing the first or second cycle of IVF or intracytoplasmic s...

Gene, 2018

Tripterygium glycosides (TGs) are chemotherapeutic drugs and immunosuppressant agents for the tre... more Tripterygium glycosides (TGs) are chemotherapeutic drugs and immunosuppressant agents for the treatment of cancer and autoimmune diseases. We have previously reported that TGs induces premature ovarian failure (POF) by inducing cytotoxicity in ovarian granulosa cells (OGCs). Hence, we report that TGs suppress the expression of the Hippo-YAP/TAZ pathway in murine OGCs in vitro and in vivo. We found that the expressions of miR-181b, miR-15a, and miR-30d, were elevated significantly in the POF. Luciferase reporter assays confirmed that miR-15a targets Lats1 through a miR-15a binding site in the Lats1 3′UTR. Overexpression of miR-15a in mOGCs not only inhibited proliferation and growth of mOGCs, but also induced aging of mOGCs. Western blot and qPCR analysis indicated that miR-15a suppresses the expression of the Hippo-YAP/TAZ pathway in mOGCs. When the exogenous miR-15a was expressed on mouse OGCs, it could elevate the cytotoxicity effect of TG on mOGCs. We conclude that tripterygium glycosides promote cytotoxicity, senescence, and apoptosis in ovarian granulosa cells by inducing endogenous miR-15a expression and inhibiting the Hippo-YAP/TAZ pathway.

A pannexin 1 channelopathy causes human oocyte death

Science Translational Medicine, 2019

Inherited dominant mutations in PANX1 cause female infertility characterized by oocyte death.

Human reproduction (Oxford, England), Jan 29, 2017

Can dydrogesterone (DYG) be used as an alternative progestin in a progesterone primed ovarian sti... more Can dydrogesterone (DYG) be used as an alternative progestin in a progesterone primed ovarian stimulation (PPOS) protocol? DYG can be used as an appropriate alternative progestin in a PPOS protocol. PPOS is a new ovarian stimulation regimen based on a freeze-all strategy that uses progestin as an alternative to a GnRH analog for suppressing a premature LH surge during the follicular phase. Medroxyprogesterone acetate (MPA) has been successfully used as an adjuvant to gonadotrophin in the PPOS protocol. However, the use of MPA may lead to stronger pituitary suppression and thus may require a higher dosage of hMG and a longer duration of ovarian stimulation than that of conventional ovarian stimulation protocol. A prospective RCT including 516 patients was performed between November 2015 and November 2016. Computerized randomization was conducted to assign participants at a 1:1 ratio into two treatment groups: an hMG + DYG group (260 patients) or an hMG + MPA group (256 patients) foll...

Clinical endocrinology, Jan 16, 2017

To compare the endocrinological profiles, cycle characteristics and pregnancy outcomes of progest... more To compare the endocrinological profiles, cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) with or without clomiphene citrate (CC) supplementation in normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Prospective randomized controlled study. A total of 320 infertile women undergoing IVF/ICSI. Medroxyprogesterone acetate (MPA) and human menopausal gonadotropin (hMG) were simultaneously administered on menstrual cycle day 3. The women were randomized into two equal groups with or without CC supplementation. The primary outcome measure was the percentage of women with profound pituitary suppression (luteinizing hormone (LH) < 1.0 IU/L on the trigger day). The secondary outcomes were endocrinological profiles, cycle characteristics and pregnancy outcomes. The percentage of women with profound pituitary suppression was significantly lower in the study group (hMG + MPA + CC) than in the cont...

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2017

To apply the three-dimensional (3D) hysterosalpingo-contrast sonography (HyCoSy) with perfluoropr... more To apply the three-dimensional (3D) hysterosalpingo-contrast sonography (HyCoSy) with perfluoropropane-albumin microspheres as contrast agents and normal saline injections into the pelvic cavity for assessment of the tubal patency and adhesions of fimbrial parts. Fifty-five infertile female patients were recruited to undergo 3D HyCoSy with normal saline injected into the pelvic cavity, in which the tubal patency was observed by visualizing the spillage of contrast agents from the fimbriae, and the fimbrial adhesion was confirmed by the finger-like projections of the fimbriae and their floating and moving status. Of the 55 patients, bilateral tubal patency was observed in 44 (80.0%), unilateral tubal patency and the other partial occlusion in 7 (12.7%), unilateral partial occlusion and the other complete occlusion in 3 (5.4%), and bilateral complete occlusion in 1 (1.8%). The fimbrial parts were observed in 105 fallopian tubes, among which 101 were seen with the finger-like fimbriae ...

Scientific Reports, 2017

This study investigated the use of medroxyprogesterone acetate (MPA) or a short protocol for cont... more This study investigated the use of medroxyprogesterone acetate (MPA) or a short protocol for controlled ovarian hyperstimulation (COH) in patients with advanced endometriosis who have normal ovarian function, and to compare cycle characteristics and pregnancy outcomes after frozen-thawed embryo transfer (FET). This was a retrospective case-control study of 244 patients with advanced endometriosis undering COH. The patients were allocated to three groups: the surgery group with MPA COH (62 patients, 71 IVF/ICSI cycles, 78 FET cycles); the aspiration group with MPA COH (85 patients had ovarian "chocolate" cysts (>3 cm) aspirated, 90 IVF/ICSI cycles, 76 FET cycles); and the short protocol group (97 patients, 101 IVF/ICSI cycles, 51 FET cycles). The results showed that higher rates of mature oocyte, D3 high quality embryo, hMG dose were observed in the two study groups using MPA compared with the short protocol. The number of >10-14 mm follicles on the trigger day, D3 top-quality embryos, viable embryos, rates of cancellation, fertilization, implantation, pregnancy outcomes were similar among the three groups. The oocytes, embryos, and pregnancy outcomes were not influenced by endometrioma surgery or presence of endometrioma. MPA COH could be effective for women with ovarian advanced endometriosis who had normal ovarian function. Endometriosis is an estrogen (E 2)-dependent condition characterized by endometrial tissue located outside of the uterus. It affects approximately 10% of women in the United States and 20-40% of women seeking infertility evaluation 1-3. Even mild endometriosis may have a direct negative effect on fertility because of its impact upon oocyte development, embryogenesis, or implantation 4-9. Nevertheless, the exact mechanisms are unknown 5. During IVF cycles, controlled ovarian hyperstimulation (COH) using gonadotropin-releasing hormone agonist (GnRH-a) may suppress some of the negative effects of endometriosis on pregnancy 10. Prolonged GnRH-a treatment prior to IVF may improve fertility rates in advanced endometriosis 11,12 , but supra-physiological concentrations of E 2 and progesterone could affect endometrium receptivity and pregnancy outcomes of patients with endometriosis 13,14. Whether women with endometriosis have a reduced pregnancy rate compared with women with tubal factor infertility 15-18 or not 19-25 remains controversial. Progestins have been used for endometriosis therapy for more than 40 years. It is believed that they act as progesterone receptor agonists, but their pharmacological actions are still not understood 9,26. Progestins create a low E 2 environment and inhibit the growth of ectopic endometrium. Progestins have good tolerability, minor metabolic effects, and low cost. Fechner et al. 27 suggested that progestins can regulate local E 2 biosynthesis in women with endometriosis. Progestin may yield a greater proportion of mature oocytes capable of fertilization

Journal of Fertilization: In Vitro - IVF-Worldwide, Reproductive Medicine, Genetics & Stem Cell Biology, 2013

JFIV, an open access journal J o u rn al of Fe rt il iz a tio n: In V it ro-I V F-Worldw id e

Oncotarget, 2017

Progestin-primed ovarian stimulation (PPOS) protocol has recently been demonstrated to be an nove... more Progestin-primed ovarian stimulation (PPOS) protocol has recently been demonstrated to be an novel regimen for preventing premature LH surges during controlled ovarian hyperstimulation (COH) in combination with frozen-thawed embryo transfer (FET). Our prospective controlled study was to explore the effect of human chorionic gonadotropin (hCG) contained in human menopausal gonadotropin (hMG) on the clinical outcomes in normalovulatory women undergoing COH with PPOS. A total of 180 patients were allocated into three groups according to the gonadotropin (Gn) used: group A (human menopausal gonadotropin, hMG-A), group B (hMG-B) or group C (follicle stimulating hormone, FSH). The primary outcome measured was the number of oocytes retrieved. The number of oocytes retrieved in group A B C was 10.72±5.78 11.33±5.19and13.38±8.97, respectively, with no statistic significance (p>0.05). Other embryological indicators were also similar (p>0.05). The concentration of serum and urinary β-hCG on the trigger day in group A and B were not associated with embryo results (p>0.05). There was no significant differences in the clinical pregnancy rate (41.67% vs. 51.56% vs. 39.51%, p>0.05) and implantation rate (31.58%vs. 34.75%vs.25.33%) after FET among the three groups. Thus the clinical characteristics were not affected by the hCG contained in hMG in normalovulatory women treated with PPOS.

Scientific reports, Jan 7, 2017

Among women undergoing IVF, high BMI negatively affects pregnancy outcomes when using the convent... more Among women undergoing IVF, high BMI negatively affects pregnancy outcomes when using the conventional ovary stimulating protocols combined with fresh embryo transfer. Therefore, finding a proper treatment for these high BMI women is more important and urgent when obesity is prevalent. In our study, we reported a retrospective study of 4457 women who were divided into normal BMI group (18.5 kg/m(2)-24.9 kg/m(2)) and high BMI group (≥25 kg/m(2)) undergoing 4611 IVF treatment cycles with frozen embryo transfer (FET). We found the high BMI group originally had the poor oocytes performance, but after FET they got the similar pregnancy outcomes as the normal BMI group. Then under FET we analyzed the IVF outcomes of our new progestin-primed ovary stimulation (PPOS) protocol, indicating that the hMG + MPA (4 or 10 mg/d) groups had the obvious better pregnancy results than the conventional short group in the high BMI group, and binary logistic regression analysis showed the hMG + MPA (10 mg...

Molecular medicine reports, Jan 14, 2017

Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstru... more Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstruction and rejuvenation. However, it is limited by the low survival rate of the transplanted fat, due to the slow revascularization of such grafts. Previous studies have demonstrated that bone marrow mesenchymal stem cell‑derived extracellular vesicles (BMSC‑EVs) are proangiogenic. The present study aimed to investigate whether BMSC‑EVs could improve the survival of transplanted fat grafts. Extracellular vesicles were isolated from the supernatant of cultured rat bone marrow mesenchymal stem cells, and characterized by flow cytometry and scanning electron microscopy. Their proangiogenic potential was measured in vitro using tube formation and cell migration assays. Subsequently, human fat tissue grafts, alongside various concentrations of BMSC‑EVs, were subcutaneously injected into nude mice. A total of 12 weeks following transplantation, the mice were sacrificed and the grafts were harve...

Scientific reports, Aug 8, 2016

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the o... more To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P &lt...

Fertility and sterility, 2016

To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluat... more To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with suboptimal response to GnRH-a. A retrospective data analysis. A tertiary-care academic medical center. A total of 8,092 women undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles. All women underwent hMG + medroxyprogesterone acetate (MPA)/P treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were cryopreserved for later transfer. The rates of oocyte retrieval, mature oocytes, fertilization, and the number of oocytes retrieved, mature oocytes, and embryos frozen. In total, 2.71% (243/8,970) of patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH ≤15 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%), fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2....

Fertility and sterility, Jan 22, 2016

To investigate flexibility in starting controlled ovarian stimulation at any phase of the menstru... more To investigate flexibility in starting controlled ovarian stimulation at any phase of the menstrual cycle in infertile women undergoing treatment with assisted reproduction. Retrospective cohort study. Academic tertiary-care medical center. At total of 150 infertile patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Ninety of the women also underwent frozen embryo transfer (FET) procedures. Depending on the phase of the menstrual cycle when ovarian stimulation was started, three groups of patients were identified, namely: conventional group (ovarian stimulation started in the early follicular phase), late follicular phase group, and luteal phase group. When dominant follicles were observed, final oocyte maturation was triggered with the use of GnRH agonist and hCG. In all three groups, viable embryos were cryopreserved for subsequent transfer. Primary outcome: number of mature oocytes retrieved. fertilization rate, viable embryo ra...

Clinical endocrinology, Jan 25, 2015

We have previously reported a new luteal-phase ovarian stimulation (LPS) strategy for infertility... more We have previously reported a new luteal-phase ovarian stimulation (LPS) strategy for infertility treatment. The purpose of this study was to systematically assess the efficiency and safety of this strategy by comparing it with conventional ovarian stimulation protocols. Retrospective cohort study. Patients with normal ovarian reserve undergoing ovum pick-up (OPU) cycles between April 2012 and September 2013 were enrolled: 708 patients underwent the LPS protocol compared with 745 patients who underwent the mild treatment protocol and 1287 patients who underwent the short-term protocol. Number of mature oocytes retrieved and top-quality embryos obtained, implantation rate, pregnancy rate, live birth and ongoing pregnancy rate, and neonatal outcomes. The numbers of mature oocytes retrieved and top-quality embryos obtained per OPU cycle were significantly increased in the LPS group (10.9±7.6 and 4.6±4.3, respectively) compared with the mild treatment group (3.7±3.0 and 1.8±1.8, respect...

PloS one, 2015

The goal of this study is to elucidate the effects of 17β-estradiol and TCDD (2,3,7,8-tetrachloro... more The goal of this study is to elucidate the effects of 17β-estradiol and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on macrophage phenotypes in the endometriotic milieu. Co-culture of endometrial stromal cells (ESCs) and U937 cells (macrophage cell line) was performed to simulate the endometriotic milieu and to determine the effects of 17β-estradiol and/or TCDD on IL10, IL12 production and HLA-DR, CD86 expression by U937 macrophages. We found that combining 17β-estradiol with TCDD has a synergistic effect on inducing M2 activation when macrophages are co-cultured with ESCs. Moreover, the combination of 17β-estradiol and TCDD significantly enhanced STAT3 and P38 phosphorylation in macrophages. Differentiation of M2 macrophages induced by 17β-estradiol and TCDD were effectively abrogated by STAT3 and P38MAPK inhibitors, but not by ERK1/2 and JNK inhibitors. In conclusion, 17β-estradiol and TCDD in the ectopic milieu may lead to the development of endometriosis by inducing M2 polarizati...