A comprehensive evaluation of progestin-primed ovarian stimulation protocol in patients with or without PCOS undergoing in vitro fertilization

Progestin-primed ovarian stimulation (PPOS) regimen was established for assisted reproduction. However, its feasibility and outcomes in polycystic ovary syndrome (PCOS) patients need further evaluation. The outcomes of infertile patients with PCOS (study group) and normal ovaries (control group with unexplained infertility and tubal factor infertility) who underwent PPOS and IVF/ICSI protocol were retrospectively studied. The baseline information, primary, and secondary outcomes of patients were collected. The dynamic changes of hormones were closely monitored. 198 PCOS patients and 374 controls were included in this study. After controlled ovarian hyperstimulation (COH), 15 oocytes were retrieved from PCOS patients on average, which was more than those from the controls (p < 0.001). The oocytes and embryos obtained from the PCOS patients exhibited better developmental potential as the number of fertilized oocytes, cleaved embryos, top-quality embryos, viable embryos, cryopreserved embryos, the rate of fertilization, and viable embryo per oocyte retrieved in PCOS patients were significantly higher than those in the controls (all p < 0.001). No significant difference between the two groups was identified regarding the primary outcome, ongoing pregnancy, and other secondary outcomes. No moderate to severe ovarian hyperstimulation syndrome (OHSS) was diagnosed in either group. With the proposed PPOS protocol, the quantity, quality, developmental potential of oocytes, and embryos obtained from PCOS patients were superior to those from controls. The protocol was efficient and safe in terms of pregnancy, obstetric, and perinatal outcomes. OHSS was effectively mitigated in the patients, with or without PCOS, who underwent COH.     

年轻POR女性拮抗剂方案与长方案的新鲜移植周期临床妊娠结局的比较分析

目的:比较分析拮抗剂方案与长方案对年轻卵巢低反应(POR)女性体外受精(IVF)新鲜移植周期临床妊娠结局的影响,以探讨拮抗剂方案的应用价值。方法:回顾性分析2014年1月至2017年6月在广东省妇幼保健院生殖中心行体外受精-胚胎移植(IVF-ET)治疗的204例妇女213个IVF新鲜移植周期的临床资料。按随机数字表法分为拮抗剂组83例(84治疗周期)与长方案组121例(129治疗周期),比较两组一般资料、实验室资料、促排卵资料及妊娠结局的差异。结果:拮抗剂组的窦卵泡计数(AFC)、抗苗勒氏激素(AMH)水平、促性腺激素(Gn)使用天数、Gn总量、HCG日雌二醇(E2)水平、HCG日内膜厚度、移植日内膜厚度、获卵数、成熟卵子数及正常受精数低于长方案组,基础FSH/LH、Gn启动量高于长方案组(P0.05),但两组优质胚胎数、移植胚胎数、移植囊胚比例、冷冻胚胎数、胚胎种植率及早期自然流产率比较均无统计学差异(P0.05)。拮抗剂组和长方案组的临床妊娠率较高,分别为58.14%和63.10%,但是两组临床妊娠率比较无统计学差异(P0.05)。结论:给予年轻POR患者两种方案均可获得较满意的IVF新鲜移植周期临床妊娠结局,拮抗剂方案获卵数较长方案少,但是其优势在于Gn使用量更少,使用时间更短。     

Recombinant versus urinary follicle-stimulating hormone in the low-dose regimen in anovulatory patients with polycystic ovary syndrome: a safer and more effective treatment.

BACKGROUND: We studied polycystic ovarian syndrome (PCOS) in fifty 25- to 37-year-old women who failed to conceive with clomiphene citrate treatment. METHODS: Twenty patients were submitted to treatment with low-dose (75 IU) urinary FSH (uFSH) in order to achieve ovulation and 30 patients were treated with recombinant FSH (rFSH) according to the same protocol. RESULTS: Ovulation was achieved in 75 and 97% of the cycles after uFSH and rFSH, respectively (p < 0.02). The length of treatment needed to achieve ovulation, the number of ampules given and dose per kilogram were significantly lower in the rFSH group. Mild ovarian hyperstimulation syndrome (OHSS) was observed in 9 uFSH cycles, whereas only 1 of the women treated with rFSH developed an OHSS (1/38 vs. 9/36; p < 0.01). CONCLUSION: rFSH is more efficient than uFSH in inducing ovulation in PCOS patients. The high prevalence of ovulatory cycles using a lower dose guaranteed greater safety of treatment and significantly reduced the incidence of OHSS.     

Successful pregnancy following the transfer of re-vitrified twice-warmed embryos due to the forced cancellation of the primary FET: A case report

PurposeEmbryo cryopreservation represents a central procedure in in-vitro fertilization (IVF) programs. This report documents a Case of a successful pregnancy following the replacement of embryos that had to be re-vitrified due to the forced cancellation of the frozen embryo-transfer (FET).Principle resultsThe 37- year-old patient was referred to our Assisted Reproductive Technology (ART) unit for idiopathic infertility and recurrent implantation failures. The collection cycle resulted in 8 grade-A cleavage embryos (8–10 blastomeres), that were all vitrified to prevent ovarian hyperstimulation syndrome (OHSS). The first frozen embryo transfer (FET) ended in a biochemical pregnancy and the second in an ectopic pregnancy. In the third attempt, three embryos were warmed but the provider could not complete the transfer due to cervical stenosis. The two surviving embryos were therefore re-vitrified. The final FET attempt, 4 months later, was successful and ended with the live birth of a healthy female baby.ConclusionsThe transfer of re-vitrified twice-warmed embryos may represent a possible option when embryo transfer cannot be performed.     

Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol

Study Question

What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E₂) levels?

Summary Answer

The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E₂) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm.

What Is Known Already

In comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1–2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol.

Study Design, Size, Duration

From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E₂ on the day of hCG administration were known were included in the analyses.

Participants/Materials, Setting, Methods

The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E₂ levels on the day of (hCG), and a combination of both, were determined.

Main Results and the Role of Chance

The optimal threshold of follicles ≥ 11 mm on the day of hCG to identify those at risk of moderate to severe OHSS was 19 (sensitivity and specificity 62.3% and 75.6%, respectively) and for severe OHSS was also 19 (sensitivity and specificity 74.3% and 75.3%, respectively). The positive and negative predictive values were 6.9% and 98.6%, respectively, for moderate to severe OHSS, and 4.2% and 99.5% for severe OHSS.

Limitations, Reasons for Caution

This was a retrospective analysis of combined data from three trials following ovarian stimulation with two different gonadotropins.

Wider Implications of the Findings

For patients with 19 follicles or more ≥11 mm on the day of hCG, measures to prevent the development of OHSS should be considered. Secondary preventive measures include cycle cancellation or coasting, use of a GnRH agonist to trigger final oocyte maturation in place of hCG and a freeze all strategy.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00702845","term_id":"NCT00702845"}}NCT00702845{"type":"clinical-trial","attrs":{"text":"NCT00696800","term_id":"NCT00696800"}}NCT00696800{"type":"clinical-trial","attrs":{"text":"NCT00696878","term_id":"NCT00696878"}}NCT00696878     

Sperm DNA adducts impair fertilization during ICSI but not during IVF

Many studies emphasize the influence of the status of spermatozoal nucleus on fertilization, mainly with regard to DNA fragmentation. This study was undertaken to analyze the influence of DNA adducts content in spermatozoa on fertilization during assisted reproduction. Ovarian hyperstimulation, oocyte retrieval and laboratory work-up in 61 IVF (in vitro fertilization) and 118 ICSI (intracytoplasmic sperm injection) first cycles were performed according to the same protocol. Semen analysis was made according to WHO Manual (1999). DNA adducts assay in spermatozoa was performed by 32Ppostlabeling method. In total 331 fertilizable oocytes were obtained during IVF and 659 during ICSI. Both groups differed significantly by sperm count, motility and morphology but not by the concentration of DNA adducts in spermatozoa (0.0306 +/- 0.0217 in IVF versus 0.0373 +/- 0.0321 in ICSI). The fertilization rate during IVF was significantly influenced by sperm count (p=0.0002) and motility (p=0.0037) but not by DNA adducts concentration (p=0.30528), whereas during ICSI was positively influenced by sperm motility (p=0.04669) and negatively by DNA adducts concentration (p=0.00796). DNA adducts concentration in spermatozoa significantly negatively influences fertilization rate during ICSI, but not during IVF.     

Is the GnRH Antagonist Protocol Effective at Preventing OHSS for Potentially High Responders Undergoing IVF/ICSI?

Objective

To determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders.

Methods

A total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared.

Results

The duration of stimulation, E₂ level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05).

Conclusions

Our study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates.     

Body mass index and basal androstenedione are independent risk factors for miscarriage in polycystic ovary syndrome

Background

There is limited literature investigating the effects of body mass index (BMI) and androgen level on in vitro fertilization (IVF) outcomes with a gonadotropin-releasing hormone (GnRH)-antagonist protocol in polycystic ovary syndrome (PCOS). Androgen-related variation in the effect of body mass index (BMI) on IVF outcomes remains unknown.

Methods

In this retrospective study, 583 infertile women with PCOS who underwent IVF using the conventional GnRH-antagonist protocol were included. Patients were divided into four groups according to BMI and androgen level: overweight- hyperandrogenism(HA) group, n?=?96, overweight-non-HA group, n?=?117, non-overweight-HA group, n?=?152, and non-overweight-non-HA group, n?=?218.

Results

A significantly higher number of oocytes were retrieved, and the total Gn consumption as well Gn consumption per day was significantly lower, in the non-overweight groups than in the overweight groups. The number of available embryos was significantly higher in the HA groups than in the non-HA groups. Clinical pregnancy rate was of no significant difference among four groups. Live-birth rates in the overweight groups were significantly lower than those in non-overweight-non-HA group (23.9, 28.4% vs. 42.5%, P<0.05). The miscarriage rate in overweight-HA group was significantly higher than that in non-overweight-non-HA group (45.2% vs. 14.5%, P<0.05). Multivariate logistic regression analysis revealed that BMI and basal androstenedione (AND) both acted as significantly influent factors on miscarriage rate. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis for BMI and basal AND on miscarriage rate were 0.607 (P?=?0.029) and 0.657 (P?=?0.001), respectively, and the cut-off values of BMI and basal AND were 25.335?kg/m² and 10.95?nmol/L, respectively.

Conclusions

In IVF cycles with GnRH-antagonist protocol, economic benefits were seen in non-overweight patients with PCOS, with less Gn cost and more retrieved oocytes. BMI and basal AND were both significantly influential factors with moderate predictive ability on the miscarriage rate. The predictive value of basal AND on miscarriage was slightly stronger than BMI.

     

Roles of kisspeptin in IVF/ICSI-treated infertile women and in human granulosa cells

Kisspeptin, a crucial central regulator of reproduction, has been used as a trigger in in vitro fertilization (IVF) treatment. This study aimed to investigate the roles of kisspeptin in IVF treatment in infertile females (n = 30); and in steroidogenesis in human granulosa-like tumor cell line (KGN). In the human study, blood was collected at three time points including (1) the beginning of gonadotropin stimulation (Phase I), (2) around eight days after gonadotropin stimulation (Phase II), and (3) on the day of ovum pick-up (Phase III). Follicular fluid (FF) was collected at Phase III. Serum human chorionic gonadotropin (hCG) was measured 15 days after embryo transfer and fetal heart beats were determined around 42 days of menstrual cycle to classify the subjects into successful and unsuccessful groups. FF kisspeptin levels were higher in successful compared with unsuccessful subjects (P < 0.01). Kisspeptin levels were significantly higher in FF than in serum in successful subjects (P < 0.05) but were comparable in unsuccessful subjects. Serum kisspeptin was comparable among three phases in the successful group but its levels in Phase III were significantly lower compared with Phase I in the unsuccessful group (P < 0.01). Serum kisspeptin in Phase II/III had positive correlations with serum E2 in Phases II and III and the outcomes of IVF/intracytoplasmic sperm injection (ICSI) treatment including serum hCG levels. For the cell experiment (n = 3), kisspeptin treatment in the presence of FSH together with IGF-1 enhanced CYP19A1 (aromatase) mRNA expression compared with control. FSH alone increased aromatase concentrations in the supernatant compared with control and kisspeptin at the dose of 10^-2 mmol/L with FSH enhanced aromatase concentrations in the supernatant compared with FSH alone (P < 0.001 all). In conclusion, kisspeptin enhanced aromatase expression and secretion and was associated with positive outcomes of IVF/ICSI treatment. Further studies regarding supplementation of kisspeptin could reveal its beneficial effects on IVF/ICSI treatment.     

Comparison of follicular fluid and serum levels of Inhibin A and Inhibin B with calculated indices used as predictive markers of ovarian hyperstimulation syndrome in IVF patients

Background  

Ovarian Hyperstimulation Syndrome (OHSS) is a severe health complication observed in some patients undergoing hormonal stimulation during IVF. Presence of OHSS is often associated with a high count of growing follicles responding to FSH hyperstimulation. However, the number of responding follicles may not be sufficient enough to predict the onset and severity of OHSS. The aim of this study was to find whether follicular fluid (FF) and serum concentrations of Inhibin A and Inhibin B in patients undergoing IVF treatment may serve as a predictor of OHSS status independent of the growing follicles count.     

Early onset of cabergoline therapy for prophylaxis from ovarian hyperstimulation syndrome (OHSS): A potentially safer and more effective protocol

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ± 2730 and the mean number of retrieved oocytes was 19.7 ± 7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.     

Defining human embryo phenotypes by cohort-specific prognostic factors

Background

Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes.

Methodology/Principal Findings

We retrieved data for all 1117 IVF cycles performed in 2005 at Stanford University Medical Center, and further analyzed clinical data from the 665 fresh IVF, non-donor cycles and their associated 4144 embryos. Thirty variables representing patient characteristics, clinical diagnoses, treatment protocol, and embryo parameters were analyzed in an unbiased manner by regression tree models, based on dichotomous pregnancy outcomes defined by positive serum ß-human chorionic gonadotropin (ß-hCG). IVF cycle outcomes were most accurately predicted at ∼70% by four non-redundant, embryo cohort-specific variables that, remarkably, were more informative than any measures of individual, transferred embryos: Total number of embryos, number of 8-cell embryos, rate (percentage) of cleavage arrest in the cohort and day 3 follicle stimulating hormone (FSH) level. While three of these variables captured the effects of other significant variables, only the rate of cleavage arrest was independent of any known variables.

Conclusions/Significance

Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort.     

Intrauterine Instillation of Human Chorionic Gonadotropin with Intrauterine Insemination Catheter Around the Golden Time of Embryo Transfer Does Not Improve In Vitro Fertilization /Intracytoplasmic Sperm Injection Outcomes in Infertile Women: A Randomized Controlled Trial

Background:We set out to explore the effect of intrauterine human chorionic gonadotropin (hCG) instillation by intrauterine insemination (IUI) catheter before embryo transfer (ET) on assisted reproductive technologies (ART) outcomes of infertile women.Methods:One hundred women with infertility who were scheduled for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included in the study. They were randomly devoted to two groups: experimental (n= 50) and control (n= 50). In the experimental group, 500 IU hCG passed into the internal cervical orifice via IUI catheter within 15 minutes before the transfer of fresh or vitrified cleavage-stage embryos. The control group underwent the same ET procedure without prior injection of hCG. Results:None of the outcomes showed a statistically significant difference between the two groups. In the intervention and control groups, respectively, biochemical pregnancies rates were 26% and 18%, implantation rates were 13.5% and 8.6%, clinical pregnancies rates were 22% and 14%, ongoing pregnancies rates were 18% and 14%, and live birth rates were 14% and 12%.Conclusion:Intrauterine injection of hCG via IUI catheter is not recommended in a clinical routine setting at this stage. Future efforts are warranted to further refine the applicability of this modality.Key Words: Assisted reproductive technologies, Embryo transfer, Human chorionic gonadotropin, Intrauterine insemination catheter, Randomized clinical trial     

The Effects of Selenium Supplementation on Gene Expression Related to Insulin and Lipid in Infertile Polycystic Ovary Syndrome Women Candidate for In Vitro Fertilization: a Randomized,Double-Blind,Placebo-Controlled Trial

This study was conducted to evaluate the effects of selenium supplementation on gene expression related to insulin and lipid in infertile women with polycystic ovary syndrome (PCOS) candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was conducted among 40 infertile women with PCOS candidate for IVF. Subjects were randomly allocated into two groups to intake either 200-μg selenium (n = 20) or placebo (n = 20) per day for 8 weeks. Gene expression levels related to insulin and lipid were quantified in lymphocytes of women with PCOS candidate for IVF with RT-PCR method. Results of RT-PCR demonstrated that after the 8-week intervention, compared with the placebo, selenium supplementation upregulated gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (1.06 ± 0.15-fold increase vs. 0.94 ± 0.18-fold reduction, P = 0.02) and glucose transporter 1 (GLUT-1) (1.07 ± 0.20-fold increase vs. 0.87 ± 0.18-fold reduction, P = 0.003) in lymphocytes of women with PCOS candidate for IVF. In addition, compared with the placebo, selenium supplementation downregulated gene expression of low-density lipoprotein receptor (LDLR) (0.88 ± 0.17-fold reduction vs. 1.05 ± 0.22-fold increase, P = 0.01) in lymphocytes of women with PCOS candidate for IVF. We did not observe any significant effect of selenium supplementation on gene expression levels of lipoprotein(a) [LP(a)] in lymphocytes of women with PCOS candidate for IVF. Overall, selenium supplementation for 8 weeks in lymphocytes of women with infertile PCOS candidate for IVF significantly increased gene expression levels of PPAR-γ and GLUT-1 and significantly decreased gene expression levels of LDLR, but did not affect LP(a).Clinical trial registration number: http://www.irct.ir: IRCT201704245623N113.     

Does day-3 LH/FSH ratio influence in vitro fertilization outcome in PCOS patients undergoing controlled ovarian hyperstimulation with different GnRH-analogue?

In an attempt to evaluate whether high basal day-3 luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio affects IVF cycle outcome in polycystic ovary syndrome (PCOS) patients undergoing ovarian stimulation with either GnRH-agonist (n = 47) or antagonist (n = 104), we studied 151 IVF cycles: 119 in patients with basal LH/FSH <2 and 32 in patients with LH/FSH ≥ 2. The PCOS with high LH/FSH ratio achieved a non-significantly higher pregnancy rate using the GnRH-agonist (50% vs 17.9%, p = 0.2; respectively), as compared to the GnRH-antagonist protocols, probably due to the ability of the long GnRH-agonist protocol to induce a prolong and sustained reduction of the high basal LH milieu and avert its detrimental effect on oocyte quality and implantation potential.     

The implication of single‐nucleotide polymorphisms in ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is an undesirable complication in the course of ovarian stimulation. This kind of stimulation is aimed at acquiring a sufficient number of high‐quality oocytes in in vitro fertilization (IVF). Whereas the predisposition to OHSS could be impacted by genetic polymorphisms in susceptible genes, the present study has been jointly conducted with an Iranian cohort to scrutinize its relevant implication. Genomic DNA was extracted from blood samples of patients with a normal ovarian response (NOR) or with OHSS. Samples were analyzed to detect polymorphisms MTHFR rs1801131, MTHFR rs1801133, AMHR2 rs2002555, LHCGR rs2293275, PGR rs10895068, and SERPINE1 rs1799889. Variations of MTHFR, AMHR2, LHCGR, and PGR genes were significantly associated with the developing OHSS. After correction for multiple analysis, this difference was not evident for PGR genotypes. The polymorphic alleles of MTHFR (rs1801131 C‐allele and rs1801133 T‐allele), AMHR2 (rs2002555 G‐allele), and LHCGR (rs2293275 G‐allele) were significantly more prevalent among patients with OHSS compared to those in the NOR group. In contrast, the minor allele of PGR single‐nucleotide polymorphism (SNP) (rs10895068, A‐allele) was more prominent among patients with a NOR than those with OHSS. No significant difference was observed in genotypes or alleles of SERPINE1 rs1799889. The observations indicated that the minor alleles of MTHFR, AMHR2, and LHCGR genes could be considered an independent risk factor in susceptibility to OHSS. Nevertheless, polymorphic allele in the PGR rs10895068 SNP contributes to preventing OHSS occurrence. Therefore, it can be argued that these genes have a significant impact on OHSS.     

Effects of dodder total flavone on polycystic ovary syndrome rat models induced by DHEA combined HCG

AimsExplore the effects of dodder total flavone on polycystic ovary syndrome (PCOS) rat models induced by dehydroepiandrosterone (DHEA) combined human chorionic gonadotropin (HCG).MethodsExcept the blank group, the rest of the rats were injected with DHEA 6 mg/100 g on the back of the neck and 1.5 IU HCG each day, for 21 consecutive days. On the 16th day of modeling, vaginal smear was performed to select the model rats, which were randomly divided into model group, dacin-35 group, large, middle and small dose dodder total flavonoids groups, and given the medicine for three weeks. At the end of the last administration, take samples, so as to calculate the ovaries and uterus indexes, measure serum LH/FSH ratio, P, PRL and INS levels, fixed the uterus and pancreas in 10% formalin solution and stained with HE to observe the morphological changes of the organs. And measure the expression of TNF-α and IGF-l proteins in ovaries by immunohistochemistry.ResultsCompared with the blank group, ovarian and uterine indexes, serum LH/FSH ratio, serum PRL and INS levels, ovary TNF-α and IGF-l protein expression were significantly increased, and significant pathological changes were observed in the uterine and pancreatic tissues in model group (P < 0.01). While the serum P level decreased significantly (P < 0.01), Compared with the model group, the ovarian and uterine indexes, serum LH/FSH ratio, serum P, PRL and INS levels, ovary TNF-α protein expression were significantly decreased in large, middle and small dose dodder total flavonoids groups (P < 0.01); The expression of IGF-1 protein was decreased and uterus pathological changes were improved in different extents (P < 0.01 or P < 0.05), pancreas pathological changes were improved significantly (P < 0.01).ConclusionPCOS rat models was successfully replicated. Dodder total flavone can protect PCOS rats induced by DHEA combined HCG by different action pathways.     

In vitro fertilization and embryo transfer in the rhesus monkey

Twenty-three rhesus monkeys were subjected to 9 days of ovarian hyperstimulation with sequential exposure to human follicle-stimulating hormone (hFSH) and then human luteinizing hormone (hLH) + hFSH. Six animals (26%) did not exhibit sustained, elevated levels of circulating estradiol, primarily due to the occurrence of a premature surge of endogenous LH (n = 4). Seventeen animals (74%) responded with supraphysiologic levels of circulating estradiol (peak value: means = 4480 pg/ml) and received human chorionic gonadotropin (hCG) on Day 10. Oocytes were collected 26 h later by aspiration of large antral follicles. Oocyte quantity (means = 18/animal) and quality (63% mature) were evaluated by in vitro fertilization (IVF), embryonic development, and embryo transfer to foster mothers. Modified conditions for the successful fertilization of oocytes used a Tyrode's augmented (TALP) medium supplemented with 0.3% bovine serum albumin (BSA). Oocytes were inseminated at the metaphase II stage with ejaculated, washed sperm (50 100 x 10(3)/ml) preexposed at ambient temperature to caffeine and dibutyryl cyclic adenosine 3'5'-monophosphate. Successful fertilization ranged from 26% to 75%. In one experiment, 5 of 11 embryos produced by IVF developed in vitro to hatched blastocysts. Embryo freezing employed a propanediol-based protocol and was applied to early cleavage-stage embryos with 100% (5 of 5) post-thaw survival. Two frozen-thawed embryos were transferred transtubally on 3 occasions into rhesus monkeys during the early luteal phase of spontaneous menstrual cycles. One pregnancy resulted, which proceeded normally to the unassisted delivery of a male offspring 170 days after the LH surge. We conclude that this sequential regimen of human gonadotropins provides a cohort of oocytes from rhesus monkeys that will complete meiotic maturation and fertilize in vitro, with embryonic development proceeding in vitro and in vivo. The production of putative antibodies to human gonadotropins, assessed by the presence of Protein A-precipitated hCG binding components in sera, limits the repeated use of monkeys in the hyperstimulation protocol. Nevertheless, this model system should facilitate further studies on oocyte maturation, fertilization, and early embryogenesis in primates.     

Risk Factors and Early Predictors for Heterotopic Pregnancy after In Vitro Fertilization

This study investigated the risk factors and early predictors for heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET). From January 2008 to January 2013, 41 cases of HP and 72 cases of intrauterine twin pregnancy after IVF-ET were recruited and retrospectively analyzed. Compared with intrauterine twin pregnancy group, the HP group had a lower basal luteinizing hormone (LH) level (P = 0.005) and more cases had a history of hydrosalpinx (P = 0.008). After 14 days of IVF-ET, the serum β-HCG (β-human chorionic gonadotropin), E2 (Estradiol) and P (Progesterone) levels were lower in HP group (P<0.001, respectively). Moreover, vaginal bleeding and abdominal pain were the significant features of HP before diagnosis (P<0.001, respectively). Further by logistic regression, serum β-hCG, P levels on the 14th day after ET, and vaginal bleeding were identified as the independent factors of HP. These results indicate that when two or more embryos transferred in IVF procedure, β-hCG, P levels on the 14th day after ET, and vaginal bleeding could be taken as predictors for HP.     

Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

ObjectiveTo determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal respondersDesignRetrospective analysisSettingUniversity infertility clinicPatientsA total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycleInterventionsWomen were classified into 4 groups according to the Bologna criteria for comparisonResultsWomen with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108).ConclusionWomen who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded.