Functioning gonadotroph adenoma with hyperestrogenemia and ovarian hyperstimulation in a reproductive-aged woman:A case report and review of literature

BACKGROUND Functioning gonadotroph adenomas are extremely rare pituitary tumors that secrete gonadotropins and exhibit distinct clinical manifestations.Here,we report a case of functioning gonadotroph adenoma in a reproductive-aged woman and discuss its diagnosis and management.CASE SUMMARY A 21-year-old female patient with abdominal pain,irregular menstruation,hyperestrogenemia,and an ovarian mass was included.Brain magnetic resonance imaging(MRI)revealed a pituitary macroadenoma,and transsphenoidal surgery relieved her clinical symptoms.Before transsphenoidal surgery,plasma CA125,estradiol levels were elevated,while prolactin,luteinizing hormone,follicle-stimulating hormone,PROG,cortisol,FT4,thyroid-stimulating hormone,para-thyroid hormone,and GH levels were maintained at normal levels.After trans-sphenoidal surgery,the patient was diagnosed with a functioning gonadotroph adenoma.During follow-up,pelvic ultrasound confirmed normal-sized ovaries in the patient,the menstrual cycle returned to regular,and her hormones were maintained within a normal range.There was no evidence of tumor recurrence after two years of follow-up.CONCLUSION Early diagnosis of functioning gonadotroph adenomas should be considered in patients with hyperestrogenism,irregular menstruation,large or recurrent ovarian cysts,and visual field defects.Pituitary MRI should be performed,and transsphenoidal surgery is recommended for the management of this disease.

Correlation of IL-1, IL-6, IL-10 Concentrations to Ovarian Hyperstimulation Syndrome and Effect of Intravenous Immunoglobulin on Ovarian Hyperstimulated Rats

Objective To investigate the correlation of interleukin（IL）-1,IL-6 and IL-10 concentrations to ovarian hyperstimulation syndrome（OHSS） and whether intravenous immunoglobulin（IVIG） has the effects on ovarian hyperstimulated rats. Methods Immature female Wistar rats were divided into control group, OHSS group （n=13） and IVIG group（n=13）. For the latter two groups, pregnancy mare serum gonadotropin（PMSG）and human chorionic gonadotropin（hCG） were given to induce OHSS, and rats in IVIG group were treated with immunoglobulin. Forty-eight hours after administration of hCG, capillary permeability was evaluated from the Evans blue dye（EB） concentration in the ovaries and the EB concentration in peritoneal irrigated fluid at 30 min after the intravenous injection of EB. Rats＇ blood samples and ovaries were obtained to be measured for IL-1, IL-6 and IL-10 by ELISA. Results In OHSS group, total weights of bilateral ovaries and the ovarian EB concentration were significantly higher than those in others（P〈0.05）. Both serum and ovarian concentrations of IL-1 were significantly higher in OHSS and IVIG groups than those in control group （P〈0.05）. The ovarian concentrations of IL-6 and IL-10 in IVIG group were significantly lower than those in control group（P〈0.05）. Furthermore, the ovarian IL-10 concentration in IVIG group was significantly lower than that in OHSS group（P〈0. 05）. Conclusion Inflammation involved IL-1 in OHSS rats plays an important role. Vascular permeability was mostly increased in ovaries of hyperstimulated rats. It appears that ovaries of OHSS rats may be the primary places of inflammation. IVIG treatment resulted in statistically significant reductions in ovaries＇ weights and ovarian vascular permeability of OHSS rats, with a decreased level of ovarian IL-10. It implys that IVIG have a beneficial effect in reducing the severity of OHSS in the experimental model maybe by restrainning IL-10.

Effect and Underlying Mechanism of Bu-Shen-An-Tai Recipe on Ovarian Apoptosis in Mice with Controlled Ovarian Hyperstimulation Implantation Dysfunction

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare’s serum gonadotrophin(PMSG), followed by 7.5 IU human chorionic gonadotrophin(HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group(NC), COH implantation dysfunction model group(COH), low dosage of Bu-Shen-An-Tai recipe group(LOW), middle dosage of Bu-Shen-An-Tai recipe group(MID) and high dosage of Bu-Shen-An-Tai recipe group(HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol(E) and progesterone(P) were determined by radioimmunoassay(RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope(TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis-related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of Eand P, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It’s helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.

Spontaneous ovarian hyperstimulation syndrome: Report of two cases

BACKGROUND Spontaneous ovarian hyperstimulation syndrome(s OHSS) is extremely rare. It can be divided into four types according to its clinical manifestations and follicle stimulating hormone receptor mutations.CASE SUMMARY Here we report two cases of s OHSS in Chinese women, one with a singleton gestation developing s OHSS in the first trimester who conceived naturally and the other with a twin pregnancy developing s OHSS in the second trimester after a thawed embryo transfer cycle. Both patients were admitted to the hospital with abdominal distension, ascites, and enlarged ovaries. Conservative treatment was the primary option of management. The first patient had spontaneous onset labor at 40 wk of gestation and underwent an uncomplicated vaginal delivery of a male newborn. The second patient delivered a female baby and a male baby by caesarean section at 35 wk and 1 d of gestation.CONCLUSION Patients with a history of ovarian hyperstimulation syndrome should be closely monitored. Single embryo transfer might reduce the risk of this rare syndrome.

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze-all strategy: A case report and review of the literature

Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.

Endometrial Mucin-1 and Pinopode in Peri-implantation Phase in Ovarian High Responders during Controlled Ovarian Hyperstimulation Cycles

Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.

Common carotid artery thrombosis and malignant middle cerebral artery infarction following ovarian hyperstimulation syndrome:A case report

BACKGROUND Arterial thrombosis is a serious and rare complication of ovarian hyperstimulation syndrome(OHSS).Herein,we describe a case of OHSS complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction after egg retrieval and before embryo transfer.CASE SUMMARY A 32-year-old female with a family history of thrombosis who was undergoing in vitro fertilization due to unexplained infertility,was admitted due to abdominal distension for 3 d and coma for 2 h.She received egg retrieval 7 d ago and embryo transfer had not yet been performed.Blood biochemical analysis showed estrogen of 15781 pmol/L.Gynecological examination showed palpable masses on both sides of the adnexal areas.Ultrasound observed enlarged ovaries and abdominal ascites.Imaging examination of the head and neck revealed fresh malignant middle cerebral artery infarction in the left side of brain and internal carotid artery as well as occlusion in the left carotid artery,internal carotid artery,and middle cerebral artery.The patient was finally diagnosed with severe OHSS,complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction.Liquid replacement,anticoagulation,vascular endothelium protection,brain protection and decompressive craniectomy were carried out.Rehabilitation training was then performed for 6 mo.At present,she has poor speaking ability and decreased muscle strength on the right side.CONCLUSION There is a risk of thrombosis during any period of OHSS.During in vitro assisted reproduction,for cases with a family history of thrombosis,hyperlipidemia and other high-risk factors,serum lipid levels should be controlled as soon as possible to improve metabolic dysfunction.When thrombosis occurs,timely and effective treatment should be performed to improve the prognosis.

Peripheral blood transcriptome analysis of patients with ovarian hyperstimulation syndrome through high-throughput sequencing

Objective:Ovarian hyperstimulation syndrome(OHSS)is a frequent iatrogenic complication that arises during assisted reproduction and accounts for approximately 30%of all in vitro fertilization cycles.Using high-throughput sequencing,we investigated the peripheral blood transcriptome of patients with OHSS.Methods:Peripheral blood samples were obtained from 15 patients in each of the OHSS high-risk and low-risk groups on the ovum pick-up day.Subsequently,high-throughput sequencing was used to obtain the peripheral blood transcriptomes of five patients each from the high-and low-risk groups.Bioinformatic tools were used for mRNA expression profile mapping and screening of differentially expressed genes(DEGs).Bioinformatics techniques were also implemented in the Kyoto Encyclopedia of Genes Genomes(KEGG)signal pathway,Gene Ontology(GO)function,and protein-protein interaction(PPI)network analyses of DEGs.Results:A total of 20,031 genes were identified and 148 were found to be differentially expressed(P<0.05,|log_(2)FC|>0.58),with 52 upregulated and 96 downregulated genes.GO and KEGG analyses indicated that these genes were involved in extracellular corpuscles(GO:0070062),plasma membrane(GO:0005886),extracellular regions(GO:0005576),immune system response(GO:0006955),PI3K-Akt signaling pathways(hsa04151),cell adhesion molecules(CAMs,hsa04514),focal adhesion(hsa04510),and complement and coagulation cascades(hsa04610).The PPI network and realtime fluorescence quantitative polymerase chain reaction(qPCR)verification predicted that complement C3,von Willebrand factor,and vascular cell adhesion protein 1 proteins are highly implicated in OHSS and may serve as potential biomarkers for future OHSS studies.Conclusion:Transcriptome analysis revealed several DEGs related to OHSS risk factors in the peripheral blood,indicating that these DEGs may be novel players in OHSS development.

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome： A Retrospective Cohort Study in Chinese Patients

Background： The effect of ovarian hyperstimulation syndrome （OH SS） on pregnancy outcomes of in vitro fertilization （IVF） patients is still ambiguous. Tbis study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. Methods： A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm deliver）,, preterm birth before 34 weeks＇ gestation, cesarean delivery, low birth weight （LBW）, and small-for-gestational age （SGA） between the two groups. Odds ratios （ORs） and 95% confidence intervals （Cls） of measure of clinical pregnancy were also analyzed. Results： The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients （91.8% vs. 43.5%, P 〈 0.001）. After controlling for drug protocol and causes of infertility, the adjusted ORs of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 （95% CI, 1.86-11.61 ） and 5.83 （95% CI, 3.45-9.86）, respectively. There were no significant differences in rates of muhiple pregnancy （4.0% vs. 3.7%） and miscarriage （16.1% vs. 17.5%） between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth （82.1% vs. 78.8%）, preterm delivery （20.9% vs. 17.5%）, preterm birth before 34 weeks＇ gestation （8.6% vs. 7.9%）, cesarean delivery （84.9% vs. 66.3%）, LBW （30.2% vs. 23.5%）, and SGA （21.9% vs. 17.6%） between the two groups. Conclusion： OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.

Yiqixue Buganshen Recipe(益气血补肝肾方) Regulates the Expression of Integrin ανβ 3 in the Endometrium of Controlled Ovarian Hyperstimulation Mice

Objective： To observe the effect of Yiqixue Buganshen recipe （益气血补肝肾方, YBR） on the expression of integrin e~ v 13 3 in the endometrium of controlled ovarian hyperstimulation mice. Methods： A total of 180 mice were divided into three groups： model group, treatment group and control group. The treatment and model groups were intraperitoneally injected with gonadotropin-releasing hormone analogue for 7 days; pregnant mare serum gonadotropin was also injected on the 7th day. After 48 h, human chorionic gonadotropin was injected. The control group was injected with an equal volume of saline at the same time. From the start of the experiment, the treatment group was intragastrically administered Jinghouzengzhi Recipe （经后增殖方） and Cuhuangti Recipe （促黄体方）. The model group and the control group were intragastrically administered an equal volume of saline. Real-time reverse transcription polymerase chain reaction and Western blotting were used to detect the mRNA and protein expression of integrin α υ β 3 in mouse endometrium. Results： Integrin α υ β 3 was expressed in mouse endometrium in all groups. Integrin α υ β 3 expression increased gradually along with pregnancy, progressing from pregnant day （Pd） 1. Integrin α υ β 3 expression significantly increased on Pd 4, then began to decrease on Pd 6. Integrin α υ β 3 expression in the treatment group was higher than in the model group, and the difference was statistically significant （P〈0.05）. The difference between the treatment group and the control group was not statistically significant （P〉0.05）. Conclusion： YBR improves endometrial receptivity, and may play an important role in embryonic implantation.

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China

Background:More and more scholars have called for the cumulative live birth rate(CLBR)of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology.This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.Methods:Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI)cycles performed between January 2013 to December 2014.A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included.The study was followed up for 4 years to observe the CLBR.The multivariable logistic regression model was used to analyze the prognosis factor,P value of<0.05 was considered statistically significant.Results:The cumulative pregnancy rate was 58.14%(10,452/17,978),and the CLBR was 49.66%(8928/17,978).The female age was younger in the live birth group when compared with the non-live birth group(30.81±4.05 vs.33.09±5.13,P<0.001).The average duration of infertility was shorter than the non-live birth cohort(4.22±3.11 vs.5.06±4.08,P<0.001).The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group(both P<0.001).Meanwhile,the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group(15.35±7.98 vs.11.35±7.60,P<0.001;6.66±5.19 vs.3.62±3.51,P<0.001,respectively).Conclusions:The women's age,body mass index,duration of infertility years,infertility factors,controlled ovarian hyperstimulation protocol,the number of acquired oocytes,and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.

Effects of gonadotropin-releasing hormone antagonists on the expression of vascular endothelial growth factor and its receptors in a rat model of ovarian hyperstimulation syndrome

Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor （VEGF） and its receptors in a rat model of OHSS. Methods An immature early OHSS rat model was established. Three ovarian stimulation protocols were used： pregnant mare serum gonadotropin/human chorionic gonadotropin （hCG） alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists （GnRHa）. Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including fit-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Results Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Conclusion Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.

Predictive Value of Serum Vascular Endothelial Growth Factor and Pigment Epithelium-derived Factor in Ovarian Hyperstimulation Syndrome

Objective To explore whether the serum concentrations of vascular endothelial growth factor （VEGF） and pigment epithelium-derived factor （PEDF） could serve as the predictors of ovarian hyperstimulation syndrome （OHSS） in patients undergoing in vitro fertilization-embryo transfer （IVF-ET）. Methods Enzyme-linked immunoadsordent assay （ELISA） was employed to measure the serum concentrations of VEGF and PEDF on the day of hCG administration, oocyte retrieval and embryo transfer, respectively. Based on OHSS classification of the criteria of Golan, 85 patients were divided into three groups. Patients in group A （n=10） showed symptoms of severe OHSS and patients in group B （n=13） suffered from moderate OHSS. The control group （group C, n=62） contained patients without symptoms of OHSS as well as patients with mild OHSS.Results In groups A, B and C, serum concentrations of PEDF on the day of hCG administration （h-PEDF）（166.54 ± 102.81 pg/ml, 159.45 ±136. 77 pg/ml, 172.05±170.95 pg/ml, P=0.48）, oocyte retrieval （o-PEDF）（176.91 ± 103.37 pg/ml, 122.52± 92.54 pg/ml, 179.82±177.47 pg/ml, P=0.27） and embryo transfer （e-PEDF）（169.02± 240.08 pg/ml, 136.80 ±139.21pg/ml, 157.38 ±222.54 pg/ml, P=0.95）, h-VEGF （175.55 ± 103.54 pg/ml, 218.84 ±179.70pg/ml, 153.39±145.06 pg/ml, P=0.36） and o- VEGF （171.93 ± 128.55 pg/ml, 220.36±149.82 pg/ml, 138. 74 ±% 139.30 pg/ml, P=0. 15） showed no significant differences. There was a statistical difference in serum concentration of e-VEGF between group A （197.04±156.63 pg/ml） and group C （110.69±49.55 pg/ml）（P=0.008）. The serum level of estradiol showed a positive correlation with the count of large follicles （r=0. 744）. The ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF were calculated and showed a clear difference among groups A, B and C （4.04±3.39, 2.10±2.14, 1.05± 4.80, P〈0.001; 4.54 5.69, 2.29 ±1.67, 0.94 ±0.59, P〈0.001; 5.43±6.16, 1.81±1.36, 2.42±2.60, P=0.04）. Conclusion While neither serum concentrations of VEGF nor PEDF can be used as an OHSS predictor, the ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF may have great predictive value.

Effects of Er'zhi Tiangui Granule (二至天癸颗粒) on Sequential Expressions of Integrin β3 and Its Ligand Osteopontin in Mouse Endometrium during Controlled Ovarian Hyperstimulation

To investigate the effects of ECzhi Tiangui Granule （二至天癸颗粒, ETG） on sequential expressions of integrin β 3 and its ligand osteopontin in the mouse endometrium during controlled ovarian hyperstimulation （COH） and implantation period. Methods： Seventy-five Mature female Kunming mice were randomly divided into 3 groups, a normal control group, a model group, and a treatment group administrated with ETG for 10 days, 25 in each group. After mated with male mice, every 5 mice were sacrified in each group at the 0, 2nd, 4th, 6th, and 8th days to take their endometrium. In-situ hybridization was used to detect the expressions of integrin β 3 and osteopontin in the endometrium. Results： mRNA expressions of integrin β 3 and osteopontin in the endometrium during implantation period showed similar time sequence rules in the treatment group to those in the normal control group; the peak values of them were a little lower in the treatment group than the normal control without significant differences. In the model group, integrin β 3 mRNA expression was higher at the 2nd day, obviously lower at the 4th and 6th days, and insignificantly lower at the 8th day; and osteopontin expression was remarkably lower at the 4th, 6th, and 8th days, compared with the normal control and the treatment groups （P〈0.05, P〈0.01）. Conclusions： COH might influence the sequential expressions of integrin β 3 and its ligand osteopontin, bring forward the integdn β 3 expression peak, impact on the cooperation of integrin β 3 and osteopontin, so as to damage the endometrial receptivity. ETG could regulate the sequential expressions of integrin β 3 and its ligand osteopontin to improve the mouse endometrial receptivity during COH.

Association of Genetic Polymorphisms of Anti-Müllerian Hormone (AMH) and Its Type II Receptor with Ovarian Hyperstimulation Syndrome

Objective To explore the association of genetic polymorphisms in the genes encoding the anti-Miillerian hormone （AMH） and its type H receptor （AMHRII） with ovarian hyperstimulation syndrome （OHSS）. Methods Using polymerase chain reaction （PCR） and DNA sequencing techniques, the exons of AMH and AMHRII were analyzed in 27 OHSS patients （OHSS group） and 22 non-OHSS patients （control group） who were applied controlled ovarian hyper- stimulation （COH）. Single nucleotide polymorphisms （SNPs） were also analyzed. Results SNPs G〉 T at position 146 of AMH exon 1 and G〉 A at position 134 of AMH exon 2 showed significant differences between the OHSS group and control group （P〈0.05）. SNP G〉 T at position 303 of AMH exon 1 showed no significant difference between the OHSS group and control group （P〉0.05）. No SNP was detected from the AMHR H exons 1 to 11 in either groups. Conclusion Genetic polymorphisms in the AMH gene may be a cause of ovarian hypersensitivity to exogenous hormone stimulation and the development of OHSS.

Hemorrhagic ovarian cyst without peritoneal bleeding in a patient with ovarian hyperstimulation syndrome: case report

Gynecologic and obstetric disorders presenting with abdominal pain are ectopic pregnancy,rupture of endometrial cysts, mature cystic teratoma and torsion of the adnexae. Hemorrhagic ovarian cysts, which included among the functional cysts, are often involved in acute abdomen leading to laparotomy intervention.

Acceleration of coasting enhances pregnancy rate in ICSI cycles at risk for ovarian hyperstimulation syndrome

Objective To assess the efficacy of adding Gn-releasing hormone antagonist（GnR HA） on the day of hC G triggering in a long luteal protocol without withholding the agonist in women who are at a risk to develop ovarian hyperstimulation syndrome（OHSS）.Methods This was a retrospective cohort study conducted upon 50 women who have elevated serum estradiol（E2） level 〉4 500 ng/L at the day of ovum triggering with hC G on a long agonist luteal protocol of controlled ovarian stimulation（COS）. When an exaggerated ovarian response was observed around day 10 of stimulation, immediately the next morning at 6 a.m. gonadotropin administration was stopped or reduced, and a single dose of ganirelix acetate（antagonist） was given sc continuation of the agonist dose hC G. Another serum E2 measurement was done at 6 p.m.（after 12 h of antagonist） then hC G, sc 250 mg and choriogonadotropin α were administered 14 h later after antagonist and documented the reduction of E2 level. Oocyte retrieval was conducted after 34-36 h of hC G administration. The measured outcomes were the level of E2 on the day of hC G injection, number of oocytes and their quality, pregnancy rate and the occurrence of OHSS and its grade in case it happened.Results The total dose for recombinant FSH was 25.3±6.4 ampoules（75 IU/ampoule） while it was 11.0±3.0 ampoules for the urinary hM G. A higher oocyte maturation rate（82.8%） and a high fertilization rate（87.8%） were observed. The mean endometrial thickness was 10.1±1.0 mm on the day of hC G triggering. The higher fertilization rate with the good endometrial thickness observed resulting in a higher pregnancy rate（78.0%, 39/50） with statistically significant（P〈0.05）. A significant reduction of E2 level was documented by a percentage around 40% before hC Ginjection. There were no reported cases of severe or moderate OHSS, however 13 cases（26%） were reported to have mild OHSS constituting.Conclusion Acceleration of coasting in cases of OHSS through treatment with GnR HA after pituitary suppression with GnR H agonist（GnR H-a） offered a novel approach to decrease E2 level, avoided cycle cancellation, and maintain excellent oocyte maturation rate, and finally result in high pregnancy rate with prevention of OHSS.

Association of Thr307Ala and Asn680Ser of Follicle-Stimulating Hormone Receptor Gene Polymorphisms with Gonadotropin Administration during Controlled Ovarian Hyperstimulation

Objective:This study is to investigate the effect of different single-nucleotide polymorphisms of follicle-stimulating hormone receptor(FSHR)gene on gonadotropin(Gn)administration dosage during controlled ovarian hyperstimulation(COH)protocol of in vitro fertilization and embryo transfer.Methods:This retrospective study included 184 Chinese infertile women in Center for Reproduction and Genetics of Suzhou Municipal Hospital from June 2012 to 2014.All of the enrolled patients were homogeneous in some basal characteristics,and they all met the eligibility criteria.Blood tests were conducted on day 3 of menstrual cycle or the day of human chorionic gonadotropin administration for hormonal profile analysis and DNA extraction.DNA sequencing was performed for polymorphism analysis.The participants were classified into threonine(Thr)/Thr,Thr/alanine(Ala),and Ala/Ala groups according to genotype at position 307,and asparagine/asparagine(Asn/Asn),Asn/serine(Ser),and Ser/Ser groups according to genotype at position 680.Logistic regression and correlation analyses were performed to identify the effect of these two polymorphisms on Gn consumption.Results:The frequency of Thr307Ala and Asn680Ser distribution was consistent with Hardy-Weinberg equilibrium(P>0.05).No significant difference was found in age,basal hormone levels for different genotype groups.Logistic regression analysis results revealed that patients with Ser680Ser genotype have a higher risk of requiring a high dose of Gn compared with patients with Asn680Asn genotype,while polymorphism of Thr307 Ala has no such effect.Conclusion:This study suggested that FSHR genotype Asn680Ser would be helpful in determining the dosage of Gn in COH;patients with Ser680Ser genotype may require higher dose of Gn.

A Delayed Ovarian Hemorrhage with Severe Ovarian Hyperstimulation Syndrome after Transvaginal Ultrasound-guided Oocyte Retrieval for in vitro Fertilization-embryo Transfer

Objective To report a case of ovarian hemorrhage after transvaginal ultrasoundguided oocyte retrieval combined with severe ovarian hyperstimulation syndrome （OHSS）. Methods A 26-year-old woman who was on therapy for infertility presented with abdominal distension and a decrease of urine after transvaginal ultrasound-guided oocyte retrieval for in vitro fertilization-embryo transfer （IVF-ET）. Initial clinical presentation, ultrasound, and lab results were consistent with the diagnosis of severe OHSS. However with 4 d conservative treatments there seemed no recovery and the patient became more serious for her hemoglobin fell from 169.0 g/L to 60.2 g/L along with more abdominal fluid and a decrease of urine. Ultrasound guided paracentesis revealed an ovarian hemorrhage, and the patient underwent emergent surgery. Results The patient underwent emergent laparotomy for oophoroplasty and preservation of ovary. She got twin pregnancy in the second frozen-thawed embryo transfer （FET） cycle and delivered two female babies. Conclusion It is important to distinguish the OHSS from ovarian hemorrhage, because the ovarian hemorrhage with hemoperitoneum requires immediate operative management, whereas OHSS is nearly always managed conservatively. Clinicians must be aware that ovarian hemorrhage may be delayed in women presenting OHSS.

Pharmacogenetic study of Asn680Ser and-29A>G in FSHR gene in Chinese women undergoing controlled ovarian hyperstimulation

The outcome of controlled ovarian hyperstimulation(COH)is various and unpredictable.According to previous studies,2 single nucleotide polymorphisms,Asn680Ser and-29A/G,have a pharmacogenetic association with ovarian response to COH.However,studies on the Asn680Ser polymorphism have yielded inconsistent conclusions and only a few studies with small sample sizes have been performed on-29A/G.The association of these 2 polymorphisms with ovarian response remains unclear.The present study evaluated the association of Asn680Ser and-29A/G genotypes with COH.A total of 414 Chinese women undergoing in vitro fertilization-embryo transfer were included.Genotypes for these single nucleotide polymorphisms were identified by high-resolution melting-curve analysis.The value of exogenous follicle-stimulating hormone dosage per oocyte divided by the body surface area(Dosage/Oocyte
Surface)was calculated for each patient as an indicator of ovarian response.The results of statistical analyses showed no association between Asn680Ser genotype and ovarian response.As for-29A/G,heterozygote individuals had more oocytes retrieved(P=0.034).Combinatorial analysis of these 2 single nucleotide polymorphisms showed that genotype A/G-Asn/Asn had lower basal-follicle-stimulating hormone and more oocytes retrieved.Analysis of genotype association with ovarian response also revealed this genotype had a significantly higher risk of developing hyper response(OR=7.86;95%CI:1.31-9.43).To some extent,there were associations between the studied polymorphisms and ovarian response;however,the power of this link is weak and has limited value for clinical prediction.