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To evaluate the safety and effectiveness of recombinant human follicle-stimulating hormone (rhFSH [Follitrope™]) in infertile women undergoing in vitro fertilization (IVF). To identify predictors of ovarian response that induce optimal clinical outcomes. This multicenter prospective study enrolled infertile women who were scheduled to undergo IVF after ovarian stimulation with rhFSH (Follitrope™) following the gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol. Predictive factors for ovarian response were identified in the GnRH antagonist group based on the number of oocytes retrieved. A total of 516 infertile women were enrolled, among whom 136 (except one who withdrew before administration) received rhFSH using the GnRH agonist protocol and 379 using the antagonist protocol. The mean number of oocytes retrieved was 13.4 in the GnRH agonist group and 13.6 in the GnRH antagonist group. The clinical pregnancy rates were 32.3% (30/93) and 39.9% (115/288) in the GnRH agonist and antagonist groups, respectively. The incidence of ovarian hyperstimulation syndrome was 1.8% and 3.4% in the GnRH agonist and antagonist groups, respectively. No other significant safety risks associated with rhFSH administration were identified. Body mass index, basal serum FSH and anti-Müllerian hormone levels, and antral follicle count were identified as predictors of ovarian response by multiple regression with backward elimination, and the final regression model accounted for 26.5% of the response variability. In real-world practice, rhFSH (Follitrope™) is safe and effective in inducing ovarian stimulation in infertile women. Patient characteristics identified as predictors can be considered to be highly related to optimal clinical outcomes.

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A 40-year-old G1 P0 L0 A1 woman was referred to our clinic with 6-year history of infertility. Before visiting the clinic, she had 3 cycles of In-Vitro Fertilization (IVF) procedures (2 cycles of Controlled Ovarian Stimulation-IVF and 1 cycle of frozen-thawed Embryo Transfer (ET)) at other clinic. She had medical history of abortion at early gestation following FET (frozen-thawed-ET). The patient had complete type of septate uterus, double cervix and longitudinal vaginal septum. Vaginal septotomy was done first and 1 month later, hysteroscopic septoplasty was followed using ballooning filled with dye. After septoplasty, we inserted ballooning and left for several days to compress septal endometrium on the septectomy area. All procedures were done in the ambulatory operating room without laparoscopy or admission. 3 months later, she had in vitro fertilization-embryo transfer (IVF-ET) and FET procedures in our clinic. She had successful pregnancy and now is at 22 weeks of gestation. New ambulatory septoplasty using dye-filled ballooning is easy, safe and minimally invasive surgery for treatment of complete septate uterus.

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This article reports a case of spontaneous ovarian hyperstimulation syndrome (OHSS) following a thawed embryo transfer cycle. OHSS, a potentially life-threatening condition, is an iatrogenic complication of controlled ovarian stimulation; therefore, it is very important to prevent and treat OHSS during treatment with ovulation-inducing agents. Despite our efforts to prevent OHSS, in this case, severe spontaneous OHSS occurred, which resulted in uncontrolled preterm labor and a preterm delivery and also persisted for 6 weeks after delivery. Freezing all embryos cannot entirely prevent the development of OHSS because OHSS can occur spontaneously. Although spontaneous OHSS remains a rare event, females with a history of OHSS may have an elevated risk for spontaneous OHSS. We suggest closely monitoring cases of pregnancy following thawed embryo transfer for early diagnosis of spontaneous OHSS and the use of conservative management.

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CONTEXT: Vitamin D maintains calcium and phosphorous homeostasis and promotes bone mineralization; however, its nonskeletal functions are increasingly being recognized. Recent evidence supports a role for vitamin D in reproductive potential, but few studies have investigated the potential effects of vitamin D on reproductive hormone biosynthesis and ovarian reserve. OBJECTIVE: The aim of this study was to determine the relationships between the serum level of vitamin D, reproductive hormone levels, and ovarian reserve in healthy nonobese women. DESIGN: This was a cross-sectional study. SETTING: The study was performed at the Fertility Center at CHA Medical Center. PARTICIPANTS: Seventy-three healthy women volunteers participated in this study. The participants were nonobese parous women with regular menstrual cycles and no history of infertility. MAIN OUTCOME MEASURES: We determined serum levels of vitamin D, steroid hormones, SHBG, ovarian reserve markers, homeostatic model assessment of insulin resistance index, and lipid profiles. RESULTS: In linear regression analysis adjusting for age, body mass index, homeostatic model assessment of insulin resistance, and lipid profile, serum vitamin D level positively correlated with total T (P < .001) and free androgen index (P < .001) but did not correlate with dehydroepiandrosterone sulfate or other steroid hormones. The spline regression-suggested relationship between 25-hydroxyvitamin D and total T was most pronounced at a 25-hydroxyvitamin D concentration greater than 13 ng/mL (ß-coefficient 2.374, 95% confidence interval 1.435-3.313). The serum vitamin D level was not associated with the levels of ovarian reserve markers. CONCLUSION: Our study revealed a positive correlation between serum vitamin D level and T level in healthy nonobese women, suggesting that vitamin D may increase fertility through the modulation of androgen activity. The possible causality of the relationship between vitamin D and T deserves further investigation.

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PURPOSE: Androgen replacement therapy has been shown to be safe and effective for most patients with testosterone deficiency. Male partners of infertile couples often report significantly poorer sexual activity and complain androgen deficiency symptoms. We report herein an adverse effect on fertility caused by misusage of androgen replacement therapy in infertile men with hypogonadal symptoms. MATERIALS AND METHODS: The study population consisted of 8 male patients referred from a local clinic for azoospermia or severe oligozoospermia between January 2008 and July 2011. After detailed evaluation at our andrology clinic, all patients were diagnosed with iatrogenic hypogonadism associated with external androgen replacement. We evaluated changes in semen parameters and serum hormone level, and fertility status. RESULTS: All patients had received multiple testosterone undecanoate (NebidoR) injections at local clinic due to androgen deficiency symptoms combined with lower serum testosterone level. The median duration of androgen replacement therapy prior to the development of azoospermia was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm concentration and serum follicle-stimulating hormone level returned to normal range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of external androgen replacement therapy in infertile men with poor sexual function can cause temporary spermatogenic dysfunction, thus aggravating infertility.

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Klinefelter syndrome is the most common genetic form of male hypogonadism, but the phenotype becomes evident only after puberty. It is characterized by infertility, small testes, sparse body and facial hair, increased body weight, gynecomastia, increased LH and FSH, and a low level of testosterone. Early recognition and treatment of Klinefelter syndrome can significantly improve the patient's quality of life and prevent serious consequences. Here, we report an infertile man with a rare variant of Klinefelter syndrome with a 47, XY, i(X)(q10) karyotype.

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BACKGROUND: Oocyte activation is a crucial step that comprises the release of the oocyte from meiotic arrest, pronuclear formation and subsequent embryo development. Oocytes are activated by repetitive increases in the intracellular concentration of free Ca(2+), [Ca(2+)](i) oscillations, which are triggered during fertilization by the introduction of the sperm-specific phospholipase C zeta 1 (PLCZ1). Recent studies have shown that sperm from patients lacking expression of PLCZ1 or expressing mutant forms of PLCZ1 fail to induce [Ca(2+)](i) oscillations or oocyte activation. We first purified recombinant human PLCZ1 (hPLCZ1) protein and evaluated its [Ca(2+)](i) oscillation activity in mouse and human oocytes with the view to investigate its application in the clinic for assisted oocytes activation in lieu of chemical agents. METHODS: Recombinant hPLCZ1 was synthesized using the Escherichia coli system, and subjected to immunoblot analysis with anti-PLCZ1 and anti-His tag antibodies. [Ca(2+)](i) oscillations by microinjection of recombinant hPLCZ1 into mouse or human oocytes were examined by [Ca(2+)](i) monitoring with Fluo 4. Ploidy of the oocytes with recombinant hPLCZ1 injection was confirmed with fluorescence in situ hybridization. RESULTS: A band of 68 kDa on recombinant protein was detected with both antibodies. Injection of recombinant hPLCZ1 induced [Ca(2+)](i) oscillations in a dose-dependent manner in both mouse and human oocytes. These oscillations, which closely resembled those initiated by the sperm upon fertilization, triggered activation and cleavage in oocytes of both species, although further development of the mice embryos was low. U73122, a PLC inhibitor, blocked the ability of hPLCZ1 to initiate oscillations. Microinjection of recombinant hPLCZ1 into ICSI-failed human oocytes rescued fertilization failure in five of eight attempts. CONCLUSIONS: Repeated [Ca(2+)](i) oscillations and oocyte activation were induced in mouse and human oocytes by microinjection of recombinant hPLCZ1 synthesized in E. Coli. Injection of recombinant protein could thus provide a biological solution for inducing artificial activation of oocytes.

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PURPOSE: To verify whether a novel protocol administering E(2) during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders. METHODS: In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/or maximal E2 level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n = 58). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n = 69) which the patients received no hormonal pretreatment. RESULTS: Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p < 0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5 ± 2.9 vs 3.2 ± 1.9; p < 0.01). A trend toward increase in number of normally fertilized embryos (2.9 ± 2.1vs 2.3 ± 1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%; p = 0.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357), although statistical significance was not achieved. CONCLUSION: Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

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The polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder, also associated with the metabolic syndrome. Serum high sensitivity C-reactive protein (hs-CRP), a marker of low-grade chronic inflammation is a potent predictor of cardiovascular events, closely linked to metabolic syndrome features and higher in patients with PCOS. However, hs-CRP in lean patients with PCOS has not been fully evaluated and few data are available. We aimed to investigate the relation between glucose intolerance and hs-CRP levels in lean patients with PCOS, and to evaluate the possible relationship between hs-CRP and PCOS by evaluating PCOS-related metabolic abnormalities in Korean women. We consecutively recruited 115 lean (BMI < 25kg/m(2)) patients diagnosed with PCOS and 103 lean healthy controls. The PCOS group was divided two groups: impaired glucose regulation (IGR) and normal glucose tolerance group (NGT). In lean patients with PCOS, hs-CRP level was higher in the IGR group than in the NGT group (0.60 ± 1.37 versus 0.18 ± 0.46, p(Bonf) = 0.023) and other metabolic risk factors were also higher in the IGR group than in the NGT group. And there were close relationships between hs-CRP level and metabolic risk factor, such as 2 h postprandial insulin level in the lean patients with PCOS.

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OBJECTIVE: To evaluate whether endometrial and subendometrial blood flow parameters measured using three-dimensional power Doppler ultrasound (3D PD-US) can predict pregnancy after IUI. DESIGN: Prospective clinical study. SETTING: Infertility center in a referral hospital. PATIENT(S): One hundred six women who underwent ovulation induction and IUI. INTERVENTION(S): A color Doppler ultrasound and a 3D PD-US examination were performed on the day of IUI. MAIN OUTCOME MEASURE(S): Pulsatility index (PI), resistance index (RI), and systolic/diastolic (S/D) ratio of uterine artery, and vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of the endometrium as well as those of subendometrial region. These measurements were analyzed in relation to IUI outcome (pregnant vs. nonpregnant). RESULT(S): The pregnant group had higher endometrium VI, FI, and VFI scores than the nonpregnant group. In contrast, the subendometrial region VI, FI, and VFI scores did not differ between the groups, nor did the uterine artery PI, RI, and S/D. Pregnancies did not occur when endometrial blood flow had not been detected. CONCLUSION(S): Three-dimensional PD-US was useful for evaluating endometrial and subendometrial neovascularization in IUI cycles. Endometrial blood flow parameters may be useful predictors for pregnancy.

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