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.

Spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma associated with primary hypothyroidism

We report an unusual case of spontaneous ovarian hyperstimulation syndrome and pituitary hyperplasia mimicking macroadenoma in an adult,non-pregnant woman.Her condition was triggered by unrecognized primary hypothyroidism,which regressed after thyroid hormone replacement therapy.This case highlights the need for clinicians and radiologists to familiarize themselves with the clinical and imaging features detected in case of these complications of primary hypothyroidism,which are not well known in the medical and radiological profession.Such improved knowledge will help avoid delays in diagnosis,progression to lifethreatening complications,and unnecessary surgery.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with≥30 Follicles Measuring≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome(OHSS),characterized by more than 30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist(GnRHa)trigger and freeze-all policy that previously have been reported.All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards.The in vitro fertilization(IVF)outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS.Moreover,patients'symptoms,reproductive honnone levels and ultrasound findings were improved significantly.This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS,especially for the patients characterized by≥30 follicles measuring≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL.Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

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.

The Influence of Cabergoline and Coasting in Prevention of the Ovarian Hyperstimulation Syndrome in Patients Undergoing IVF/ICSI-ET Treatment: A Systematic Review and Meta-Analysis

Objective: To compare the effectiveness of two methods in preventing ovarian hyperstimulation syndrome (OHSS) with cabergoline and coasting. Design: Systematic review and meta-analysis of randomized clinical trials (RCTs). Patients: Women were considered as have risk of OHSS undergoing fertility treatment. Interventions: Cabergoline, coasting. Result: There were included five RCT studies. The clinical pregnancy rate was no significantly difference between two groups (RR 1.22, 95% CI [0.86, 1.71]), implantation rate (RR 1.00, 95% CI [0.75, 1.32]), severe OHSS (RR 0.93, 95% CI [0.38, 2.31]), fertilization rate (SMD 0.70, 95% CI [-0.10, 1.50]), number of oocytes retrieved (SMD 0.80, 95% CI [0.30, 1.30]), number of embryo transfer (SMD-0.04, 95% CI [-0.24, 0.17]), E2 value on the day of HCG injection (SMD 0.21, 95% CI [-0.25, 0.68]), number of MII oocytes (SMD 0.71, 95% CI [0.32, 1.11]), abortion rate (RR 0.61, 95% CI [0.21, 1.83]), number of follicles > 17 mm on day of HCG (SMD -0.01, 95% CI [-0.26, 0.24]), number of follicles 15 - 17 mm on day of HCG (SMD -0.08, 95% CI [-0.33, 0.17]), number of follicles 10 - 14 mm on day of HCG (SMD -0.06, 95% CI [-0.31, 0.19]). Conclusion: Both cabergoline and coasting prevent the occurrence of OHSS, but no statistically significant difference between them. Compared with coasting group, a daily dose of 0.5 mg cabergoline significantly increased the number of oocytes retrieved, MII oocytes, and fertilization rate, but decreased the abortion rate.

Variations in vascular endothelial growth factor levels during ovarian superovulation and reduction of ovarian hyperstimulation incidence in young women: A prospective study

Variations in Vascular Endothelial Growth Factor (VEGF) levels were prospectively evaluated in 18 young women undergoing in vitro fertilization treatments according to the “Long Protocol” and a typical pattern of VEGF levels was recorded. A significant increase in VEGF concentrations was observed only when the follicles reached a mean diameter of 15.3 mm in concurrence with mature oocyte retrieval. Since an increase in VEGF levels is related to follicular vascularity and oocyte developpment, our study supports the approach that oocyte retrieval may be performed when follicles > 15 mm in diameter appear. Anticipating egg retrieval in young patients with an optimal ovarian reserve may decrease the incidence of severe ovarian hyperstimulation, without compromising the treatment results.

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.

Missed estradiol determination resulting in oocyte retrieval and embryo development following controlled ovarian hyperstimulation at early pregnancy: Case report

This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian hyperstimulation by gonadotropin-releasing hormone agonist long protocol. On the day of oocyte collection, a 5-week gestational sac was observed by exact sonography monitoring. However, via ultrasound guided follicle puncture, 7 oocytes were collected. After intarcytoplasmic sperm injection, 3 developed good quality embryos were cryopreserved. Moreover, the natural pregnancy was continued and finally a healthy live birth was achieved. Despite physiological hormonal changes during pregnancy, the follicular growth occurred and followed by oocyte retrieval and embryo development, subsequently.

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.

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.

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.

Pharmacotherapy Cost of Controlled Ovarian Hyperstimulation of <i>in Vitro</i>Fertilization—A Real Life Study

The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.

Clinical analyses for 93 cycles of moderate and severe ovarian hyperstimulation syndrome

Objective:To investigate the high risk factors and methods of prevention and treatment of ovarian hyperstimulation syndrome (OHSS) in assisted reproductive techniques (ART).Methods: Clinical data of 93 cycles of OHSS patients after IVF-ET treatment from Apr. 1989to Oct. 2002 were analyzed retrospectively.Results: (1) A large number of follicles stimulated, luteal phase support with HCG and pregnancy were high risk factors to induce OHSS. (2) Longer disease process, more severe symptoms and more albumins used for treatment of OHSS were commonoy observed in pregnant patients with OHSS compared with non-pregnant ones. (3) Vena dropping human serum albumin is one of the most successful treatment as plasma expanders through restoration of colloid osmotic pressure; paracentesis is necessary for critical OHSS patients with severe ascites and hydrothorax;(4) Occasionally therapeutic abortion of an early gestation may be an only way for lifesaving when all other methods have failed.Conclusions: OHSS is a serious complication of controlled ovarian hyperstimulation. Proper prevention and treatment of OHSS are important for patient safety in ART.

Follicular Aspiration Is Superior to Coasting as Effective Prophylactic Procedure against Ovarian Hyperstimulation Syndrome

Objectives: Evaluation of outcome follicular aspiration compared to coating procedure for infertile women undergoing ICSI regarding frequency and severity of ovarian hyperstimulation syndrome (OHSS). Patients & Methods: Infertile PCOS women underwent controlled ovarian stimulation with luteal phase GnRH-agonist long down-regulation protocol. Women developed serum E2 level > 4000 pg/ml and/or >20 follicles of ≥10 mm in diameter were randomly divided to receive coasting strategy (Coasting group) or TVU-guided aspiration (Aspiration group). When ≥3 follicles were ≥18 mm and serum E2 level was and 10,000 IU was administered 36 h before oocyte retrieval, and ICSI was performed 72-hr thereafter and the frequency of moderate-to-severe OHSS was determined. Results: 82 women developed criteria for categorization and 21 women (25.6%) developed moderate-to-severe OHSS;5 women of aspiration and 16 of Coasting group;with significantly (P = 0.005) lower frequency in aspiration group. Twenty women developed ascites;3 women had clinically detectable, while 17 women had US detected ascites with significantly (P = 0.039) higher frequency among women that had coasting. All other manifestations of OHSS were significantly lower with aspiration procedure. Both coasting and aspiration therapy significantly reduced serum E2 and ovarian diameter on day of hCG injection compared to estimates taken at time of categorization. Conclusion: Coasting procedure prior to hCG injection could decrease incidence of OHSS and lessens its manifestation. Follicular aspiration provided more superior results and improved outcome of these women. Any of these modalities could be provided to infertile high-risk women according to the availability of experiences and patients’ selection.

Treatment of Unexplained Infertility by Acupuncture in Natural and Control Ovarian Hyperstimulation Cycles: A Prospective Analysis

Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.

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.