Xiaona Lin

A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study ☆

OBJECTIVE To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Ashermans syndrome. STUDY DESIGN Retrospective cohort study of 107 women with Ashermans syndrome who were treated with hysteroscopic division of intrauterine adhesions. After hysteroscopic adhesiolysis, 20 patients had intrauterine balloon inserted, 28 patients had intrauterine contraceptive device (IUD) fitted, 18 patients had hyaluronic acid gel instilled into the uterine cavity, and 41 control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases, and the effect of hysteroscopic adhesiolysis was scored by the American Fertility Society classification system. RESULTS Both the intrauterine balloon group and the IUD group achieved significantly (P<0.001) greater reduction in the adhesion score than that of the hyaluronic acid gel group and control group. The efficacy of the balloon was greater than that of the IUD (P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups. CONCLUSION The insertion of an intrauterine balloon or intrauterine device is more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation.

CALCIUM-BINDING PROTEIN S100P IS HIGHLY EXPRESSED DURING THE IMPLANTATION WINDOW IN HUMAN ENDOMETRIUM

OBJECTIVE To investigate S100P expression and localization in human endometrium throughout the menstrual cycle. DESIGN Experimental study. SETTING University hospital. PATIENT(S) Eighty-four women. INTERVENTION(S) Complementary DNA (cDNA) microarray analysis was performed on human endometrium from days LH+4, LH+7, and hCG+7. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect the expression of S100P and of additional S100 family members, S100A4, S100A13, and S100A6. Immunofluorescence was used to detect the localization of S100P protein in LH+7 and LH+4 endometrium. MAIN OUTCOME MEASURE(S) Differential gene expression, levels of S100P messenger RNA (mRNA), and protein expression and immunofluorescent localization of S100P. RESULT(S) A statistical method, based on hierarchical clustering, identified genes whose expression varied at LH+7 compared with LH+4. We found that S100P was the fourth most up-regulated gene at LH+7. The S100P mRNA and protein levels were quite low during the proliferative phase and LH+4, but were elevated significantly at LH+7. The S100P expression at hCG+7 was lower than that at LH+7. However, the expression of S100A4, S100A13, and S100A6 did not vary throughout the menstrual cycle. CONCLUSION(S) S100P was specifically up-regulated during the implantation window. The underlying biological effects of S100P need further exploration.

Recurrent IVF failure is associated with elevated progesterone on the day of hCG administration

OBJECTIVE During in vitro fertilization (IVF) treatment, elevated progesterone on the day of human chorionic gonadotrophin (hCG) administration has been reported to be associated with a reduced chance of live birth. It is not known, however, if the relationship is casual or causal. In the latter situation, one would expect the incidence of elevated progesterone on the day of hCG administration to increase with the number of IVF/embryo transfer (ET) failures. The aim of this study was to investigate if the frequency of elevated progesterone on the day of hCG administration is related to the number of IVF failures. STUDY DESIGN This retrospective, observational, cohort study included a consecutive series of 6673 IVF cycles. Subjects were categorized into one of three groups: Group I, no previous IVF/ET treatment; Group II, one previous IVF/ET treatment failure; or Group III, two or more previous IVF/ET treatment failures. The main outcome measure was the proportion of cycles with elevated progesterone (>6 nmol/l) on the day of hCG administration. RESULTS After adjusting for age, oestradiol level on the day of hCG administration and number of oocytes retrieved, the proportion of women with elevated progesterone on the day of hCG administration remained significantly different between the three groups: Group I, 16.8%; Group II, 31.7%; and Group III, 39.7% (p < 0.001). CONCLUSION Elevated progesterone on the day of hCG administration is more likely in women with recurrent IVF failure. Women with two or more IVF failures are twice as likely to have elevated progesterone on the day of hCG administration as women undergoing their first IVF cycle.

Comparison of progesterone measurement on day of, and day after, HCG administration in IVF–embryo transfer cycles

The aim of this study was to identify whether progesterone measurement on the day after HCG administration has any additional clinical value, over that obtained from progesterone measurement on the day of HCG administration. This was a single-centre, non-interventional retrospective, observational, cohort of a consecutive series of 1457 ovarian stimulation cycles leading to fresh embryo transfer cycles between January 2011 and May 2013. Progesterone was found to rise and increase rapidly by about five-fold over a 24-h period. The result of logistic regression analysis suggests that progesterone measurement around the time of HCG administration is one of the three significant (P <0.001) variables affecting clinical pregnancy rate. The predictive value of progesterone measurement on the day of HCG administration could be improved by having a further measurement 24-h later. If the progesterone levels on both days were normal, the implantation rate was 36%, but if the progesterone level on both days were high, the implantation rate dropped to 22%. Progesterone measurement should be considered on the day of HCG administration and also the day after HCG administration to provide clinically useful information on whether or not embryos should be frozen and transfer deferred to a subsequent cycle.

Hypoxia Promotes Ectopic Adhesion Ability of Endometrial Stromal Cells via TGF-β1/Smad Signalling in Endometriosis

Hypoxia plays a vital role in the progression of endometriosis. Additionally, integrin-mediated aberrant adhesion is also essential for establishment of endometriotic lesions. In this study, we sought to determine the function of hypoxia in integrin-mediated adhesion of endometrial stromal cells (ESCs) in endometriosis. The expressions of adhesion molecule integrins (integrin α5, integrin αV, integrin β3, and integrin β5) were determined in 15 normal endometria and 15 paired eutopic and ectopic endometria by immunohistochemistry. Thirteen primary ESCs from patients with peritoneal endometriosis in the proliferative phase were cultured under a hypoxic (1% O2) or normoxic (21% O2) environment, and the expression levels of hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-β1, and integrins were detected by quantitative reverse transcription polymerase chain reaction and western blot. The alteration of integrins in endometriotic mouse models were also explored. Our results demonstrated that HIF-1α and integrins were highly expressed in ESCs of endometriotic lesions compared with ESCs of eutopic and normal endometrium. Hypoxia treatment significantly increased ESC adhesion abilities and integrin expression, which were positively correlated with TGF-β1 expression. Both TGF-β1 and hypoxia enhanced ESC adhesion properties, whereas hypoxia combined with TGF-β1 receptor inhibitor inhibited ESC adhesion. Knockdown of HIF-1α attenuated TGF-β1/Smad signaling activation and integrin expression and reduced ESC adhesion. Higher expression levels of HIF-1α, TGF-β1, and integrins were detected in endometriotic cysts from mice models. Our findings provide a novel insight of endometriosis that the hypoxic microenvironment stimulates ESCs to produce excessive TGF-β1 and activates the TGF-β1/Smad signaling pathway, thus enhancing integrin expression and the adhesion ability of ESCs.

Pinopode score around the time of implantation is predictive of successful implantation following frozen embryo transfer in hormone replacement cycles

STUDY QUESTION Is pinopode measurement of any prognostic value? SUMMARY ANSWER Pinopode expression was significantly associated with the occurrence of pregnancy after frozen embryo transfer. WHAT IS KNOWN ALREADY Pinopodes are expressed in the endometrium during the implantation period. Pinopode measurement has been proposed as a marker of endometrial receptivity. STUDY DESIGN, SIZE, DURATION A prospective cohort study was conducted at the Center of Reproductive Medicine, Sir Run Run Shaw Hospital, between 2014 and 2016, recruiting 172 women with infertility and undergoing frozen embryo transfer following IVF treatment. Among 172 participants, 46 women took part in the first study to quantify the daily changing pattern of pinopodes 3-7 days after the initiation of progesterone therapy in the hormone replacement cycles and the remaining 126 women with infertility participated in a study to examine the relationship between pinopode count and pregnancy outcome following frozen embryo transfer in hormone replacement cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS The mean age of participants was 29 years old. All participants received an artificial hormone replacement protocol capable of supporting successful implantation. Endometrial biopsies from 46 women were obtained 3, 4, 5, 6 and 7 days after the initiation of progesterone therapy (P + 3, n = 6; P + 4, n = 6; P + 5, n = 11; P + 6, n = 13; P + 7, n = 10, respectively). Another 126 endometrial biopsies were obtained precisely 6 days after the initiation of progesterone. Scanning electron microscopy was used to capture the pinopode images, followed by use of the image J program to quantify the count and subtype of the pinopodes. MAIN RESULTS AND THE ROLE OF CHANCE We found that at least 60 microscopic fields were necessary to achieve a reproducible result. An intra-observer variability study showed good agreement between two measurements regarding the developing pinopode (DP) subtype (r = 0.95) and the fully developed pinopode (FDP) subtype (r = 0.86) but not for the regressing (RP) pinopode subtype (r = 0.39). The proportion of DP/total pinopodes (TP) declined rapidly form day P + 4 to a minimum on day P + 6. The percentage of FDP/TP increased rapidly from day P + 4 to reach a peak on day P + 6. On the other hand, the percentage of RP/TP reached a peak on day P + 7. Participants who conceived had a significantly (P = 0.011) higher percentage of FDP/TP on day P + 6 and significantly (P = 0.005) lower percentage of DP/TP on the same day compared with participants who did not become pregnant. Using a scoring system incorporating the percentages of DP and FDP, it was found that the pregnancy rate and the embryo implantation rate of women with a high pinopode score (82.3%; 63.0%) was significantly (P = 0.001; P = 0.046) higher than that of women with a low pinopode score (53.3%; 46.7%), respectively. There remains a possibility that the observations could have arisen due to chance. LIMITATIONS, REASONS FOR CAUTION This study examined pinopode count and subtype in the HRT cycles, and it is uncertain whether the same observations apply to in natural cycles. WIDER IMPLICATIONS OF THE FNDINGS Pinopodes have been questioned as a potential marker of endometrial receptivity for many years. Our results suggested that pinopode measurement may be of value in predicting pregnancy. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by the grants from the general project of medicine and health in Zhejiang Province of China (2015KYA142; 2018KY106), the Key Research and Development Program of Zhejiang Province (2017C03022) and the National Natural Science Foundation of China (81701514).The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. TRIAL REGISTRATION NUMBER ISRCTN26300668.

Cornual Suture at the Time of Laparoscopic Salpingectomy Reduces the Incidence of Interstitial Pregnancy after In Vitro Fertilization

STUDY OBJECTIVE To investigate the effect of cornual suture at the time of laparoscopic salpingectomy on the incidence of interstitial pregnancy (IP) after in vitro fertilization (IVF). DESIGN Single-center, retrospective review (Canadian Task Force classification II-2). SETTING University hospital. PATIENTS Patients with hydrosalpinx who were treated with salpingectomy before IVF-embryo transfer and managed in our center were included in this study. INTERVENTIONS A total of 542 patients who underwent laparoscopic salpingectomy from April 2011 to March 2014 comprised group A. A total of 502 patients who underwent cornual suture at the time of laparoscopic salpingectomy from April 2014 to February 2016 comprised group B. MEASUREMENTS AND MAIN RESULTS The overall IP rate was significantly lower in group B (7/293, 2.39%) than in group A (27/373, 7.24%; p < .05). The intrauterine pregnancy and ongoing pregnancy/live birth rates were significantly higher in group B than in group A (both p < .05). All 34 patients with IP underwent laparoscopic cornuostomy and cornual repair. Seven of 11 patients with combined interstitial and intrauterine pregnancies carried the intrauterine pregnancy to term and delivered via cesarean section, whereas 4 patients underwent inevitable miscarriage. IP rupture occurred in 8 of 34 patients at a mean of 23.43 ± 2.77 days after embryo transfer. The earliest time of rupture was on day 20 after embryo transfer. CONCLUSION An optimized salpingectomy technique plays an important role in pretreatment before embryo transfer in patients with hydrosalpinx. Cornual suture at the time of salpingectomy helps reduce the risk of IP.

Laparoscopic treatment of cornual heterotopic pregnancy: A retrospective cohort study

OBJECTIVE To report on our experience of laparoscopic cornuostomy or cornual repair for cornual heterotopic pregnancy. STUDY DESIGN A single center, retrospective review of patients who were diagnosed as cornual heterotopic pregnancy, which developed after in vitro fertilization and embryo transfer (IVF/ET) between January 2009 and June 2014. All patients were managed by laparoscopic cornuostomy or cornual repair. RESULTS 14 patients were enrolled and 4 patients were finally confirmed to have a ruptured cornu. 4/4 presented as acute abdominal pain and 3/4 as metrorrhagia. The blood pressure of all the patients were stable. The earliest ruptured patient of this series happened at 23 days after IVF/ET. The hemoglobin levels of the 4 ruptured patients were significantly lower than the other patients (8.6 ± 1.8 g/dl versus 12.2 ± 1.1 g/dl, p < 0.001). Internal bleeding before operation was significantly higher in the ruptured patients than in the intact patients (1050.0 ± 369.8 ml versus 0.0 ± 0.0 ml, p < 0.001). All 14 patients were managed by laparoscopic cornuostomy or cornual repair. No one was converted to laparotomy. Post-operation pregnancy was uneventful. All neonates were delivered by cesarean section with no evident complications. CONCLUSION Laparoscopic cornuostomy or cornual repair appears to be an effective treatment for cornual heterotopic pregnancy, even in ruptured ones. These operations can be safely performed in an institution with well-trained gynecological laparoscopists with experienced support teams.

Maintenance of early pregnancy without early hormone support after frozen-thawed embryo transfer in hormone replacement treatment cycles

OBJECTIVE To report two successful pregnancies after frozen-thawed ET in discontinued hormone replacement treatment cycles. DESIGN Case report. SETTING University hospital. PATIENT(S) Two infertile patients. INTERVENTION(S) Hormone replacement treatment for endometrial preparation and frozen-thawed ET. MAIN OUTCOME MEASURE(S) Ovarian ultrasonography, serial hormone measurements of serum E2 and P, successful pregnancy, and follow-up visit. RESULT(S) One patient discontinued both E2 and P support 2 weeks after ET. The other discontinued estrogen support on the day preceding ET. No spontaneous follicle development was observed by ultrasonography, and no increase in serum P concentration was observed. Both patients became pregnant and achieved deliveries. CONCLUSION(S) These two cases show that maintenance of pregnancy is possible without early hormone support in hormone replacement treatment cycles.