Nerve growth factor (NGF) levels in follicular fluid of infertile patients undergoing to in vitro fertilization (IVF) cycle

Abstract

Objective: The aim of this study was to determine the levels of NGF in follicular fluid and serum samples, and to correlate them with some characteristics of the patients (age) and of the IVF protocol (E2 levels, number of collected oocytes, used FSHr IU) to investigate its rule in the folliculogenesis.

Methods: This study examined a sample of 78 women undergoing to FIVET/ICSI cycles since October 2011 to March 2013. NGF levels were determinated in follicular fluid (FF) and serum sample using enzyme immunoassay ELISA kit for NGF.

Results: The NGF level was significantly higher in FF (213.76?pg/ml) than in basal serum (46.47?pg/ml (p?<?0.001) and in serum sample of the pick-up day (60.75?pg/ml (p?<?0.001). In FF, the levels of NGF were positively correlated to age of women (corr.coeff. r?=?0.44) and units of FSHr used during stimulation protocol (corr.coeff r?=?0.34).

Discussion: Our results demonstrate that the FF levels are higher than the blood; so there is a local production of NGF in the ovarian follicle, important for the follicle’s growth and oocyte quality. We could also say that the increase of NGF levels is correlated to a lower ovary response, that is obviously less in the older women.     

Low-dose human chorionic gonadotropin therapy can improve sensitivity to exogenous follicle-stimulating hormone in patients with secondary amenorrhea

Objective: To assess the effect of supplementing an ovulation induction regimen of highly purified FSH with LH activity in the form of low-dose hCG therapy.

Design: Case report.

Setting: The Reproductive Endocrinology Center at the University of Bologna, Bologna, Italy.

Patient(s): A woman with weight-related secondary hypogonadotropic amenorrhea.

Intervention(s): The patient was treated first with highly purified FSH alone and then received highly purified FSH in combination with low-dose hCG therapy (50 IU/d).

Main Outcome Measure(s): Pelvic ultrasound examinations, serum E₂ levels, duration of treatment, total dose of highly purified FSH, and outcome of treatment.

Result(s): The concomitant administration of low-dose hCG and highly purified FSH markedly reduced the duration of treatment and the dose of highly purified FSH, and resulted in a quadruplet pregnancy in a patient in whom several previous ovulation induction procedures had been unsuccessful.

Conclusion(s): Supplementation of an ovulation induction regimen with an agent that has LH activity can enhance FSH-induced folliculogenesis and markedly reduce costs in women with hypogonadotropic hypogonadism. However, this increased response can be associated with complications such as multiple gestation.     

Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction

Background. Polycystic ovary syndrome (PCOS) is often characterized by chronic oligo- or anovulation (usually manifested as oligo- or amenorrhea), and hyperandrogenism. In addition, 30–40% of PCOS women have impaired glucose tolerance, and a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) seems to be implicated in the pathogenesis of insulin resistance. PCOS patients are subfertile as a consequence of such ovulatory disorders and often need drugs, such as clomiphene citrate or follicle-stimulating hormone, for ovulation induction, which increases the risk of multiple pregnancy and ovarian hyperstimulation syndrome. We hypothesized that the administration of an isoform of inositol (myo-inositol), belonging to the vitamin B complex, would improve the insulin-receptor activity, restoring normal ovulatory function.

Materials and methods. Twenty-five PCOS women of childbearing age with oligo- or amenorrhea were enrolled in the study. Ovulatory disorder due to PCOS was apparently the only cause of infertility; no tubal defect or deficiency of male semen parameters was found. Myo-inositol combined with folic acid (Inofolic®) 2 g twice a day was administered continuously. During an observation period of 6 months, ovulatory activity was monitored with ultrasound scan and hormonal profile, and the numbers of spontaneous menstrual cycles and eventually pregnancies were assessed.

Results. Twenty-two out of the 25 (88%) patients restored at least one spontaneous menstrual cycle during treatment, of whom 18 (72%) maintained normal ovulatory activity during the follow-up period. A total of 10 singleton pregnancies (40% of patients) were obtained. Nine clinical pregnancies were assessed with fetal heart beat at ultrasound scan. Two pregnancies evolved in spontaneous abortion.

Conclusion. Myo-inositol is a simple and safe treatment that is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS. This therapy did not cause multiple pregnancy.     

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.     

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.     

Unexpected pregnancy during hormone-replacement therapy in a woman with elevated follicle-stimulating hormone levels and amenorrhea.

Pregnancy in patients with hypergonadotropic amenorrhea, although previously reported, remains quite rare. Women may conceive spontaneously or following different regimens of ovulation induction, thus indicating that ovarian failure is not always permanent. The case of an 18-year-old woman with premature ovarian failure, who conceived during hormone-replacement therapy, is reported. During hormone-replacement therapy, elevated gonadotropin levels returned to the physiologically normal range. It is suggested that this restored the receptors to luteinizing hormone and to follicle-stimulating hormone, which might have been downregulated. This hypothesis is supported by previous results from clinical trials and experimental work on a rat model.     

Effect of gonadotropin-releasing hormone antagonists on intrauterine insemination cycles in women with polycystic ovary syndrome: a meta-analysis

Polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian stimulation and intrauterine insemination (COS/IUI) often face the risk of premature luteinization, which may result in lower pregnancy rate and higher miscarriage rate. This review was performed to identify if adjuvant treatment with GnRH antagonist (GnRH-ant) could effectively improve the clinical outcome of patients with PCOS undergoing COS/IUI. A literature search was conducted on the PubMed, EMBASE and Cochrane library databases. Two randomized controlled trials were included in this review, enrolling a total of 333 cycles. The patients who received GnRH-ant treatment had lower progesterone levels on the hCG day and a reduced premature luteinization rate. However, the rates of live birth, clinical pregnancy and miscarriage did not significantly differ between the GnRH-ant supplementation group and control group. In conclusion, although the existing randomized controlled trials indicate that GnRH-ant can effectively decrease the premature luteinizaton rate, evidence to support its use to improve clinical pregnancy outcomes in PCOS patients undergoing COS/IUI treatment is insufficient.     

高促卵泡激素闭经患者低骨量的临床表现

目的 了解高促卵泡激素（ＦＳＨ）卵巢性闭经患者低骨量的特点。方法 对１８例高ＦＳＨ原发产经（ＰＡ组）、１７１例高ＦＳＨ继发闭经（ＳＡ组）患者,采用放射免疫法测定血清雌二醇（Ｅ２）;生化法测定血清碱性磷酸酶（ＡＬＰ）、尿钙／肌酐（Ｃａ／Ｃｒ）比值;单光子吸收测量法测定右侧桡骨皮质骨骨密度（ＣＢＭＤ）,定量计算机断层扫描法测定腰椎松质骨骨折密度（ＴＢＭＤ）。以１８０例年龄匹配。月经正常妇女为对照（对照     

Anti-Mullerian hormone levels do not predict response to pulsatile GnRH in women with hypothalamic amenorrhea

Pulsatile GnRH is used to induce ovulation in women with hypothalamic amenorrhea (HA), but tools to predict response are lacking. We assessed whether baseline AMH levels are associated with response to pulsatile GnRH in 16 women with HA. AMH levels were compared between non-responders and women who achieved follicular development or pregnancy. Median AMH for the cohort was 2.2?ng/mL. AMH levels were undetectable or low in four women, normal in nine and high in three. Follicular development was observed in 13 (81%) women (82% of cycles) and pregnancy achieved in 10 (63%) women (29% of cycles). All four women with low or undetectable AMH had follicular response and three achieved pregnancy. Of the 12 women with normal or high AMH, 10 had a follicular response and seven achieved pregnancy. Median AMH levels were comparable in those who achieved follicular development and those who did not (2.2?ng/mL versus 1.3?ng/mL, p?=?0.78) and in those who became pregnant and those who did not (2.2?ng/mL versus 1.9?ng/mL, p?=?0.52). In summary, low AMH does not preclude response to ovulation induction in women with HA, suggesting that ovarian potential may not be the primary determinant of AMH concentrations in this population.     

Successful pregnancy and birth after sequential cotreatment with growth hormone and gonadotropins in a woman with panhypopituitarism: a new treatment protocol

Objective: To report a successful pregnancy in a woman with panhypopituitarism who received 3 months of pretreatment with growth hormone (GH) before ovulation induction. Prior attempts at ovulation induction had failed for this patient.

Design: Case report.

Setting: Department of Endocrinology.

Patient(s): A 32-year-old woman with panhypopituitarism and secondary infertility.

Intervention(s): GH (1 IU/day) alone for 3 months; during the next cycle, 1 IU/day of GH; 3 ampules of hMG per day during days 1–21; 1 ampule of hCG on day 21. GH was discontinued on day 35 when a pregnancy test was positive.

Main Outcome Measure(s): Pregnancy and delivery.

Results: Pregnancy and birth of a normal child after a single ovulation stimulation using GH and gonadotropins.

Conclusion(s): This case report suggests interest in a new protocol for follicular stimulation in women with hypopituitarism who are responding poorly to gonadotropin therapy.     

来曲唑、他莫昔芬和氯米芬治疗多囊卵巢综合征不孕疗效比较

目的比较多囊卵巢综合征(PCOS)不孕患者经纠正内分泌代谢紊乱后应用3种不同促排卵药物的效果及对子宫内膜的影响。方法选择2009年3月至2010年1月中山大学孙逸仙纪念医院妇产科生殖中心128例PCOS不孕患者,于本院行第1次促排卵,有高雄激素或胰岛素抵抗者经预处理至少3个月。随机分为3组,来曲唑44个周期、他莫昔芬40个周期和氯米芬44个周期。结果月经第10天的子宫内膜厚度,他莫昔芬组[(6.4±1.2)mm]高于来曲唑组[(5.4±1.7)mm]和氯米芬组[(5.4±1.3)mm](P=0.01);HCG日血雌二醇(E2)水平,来曲唑组[(838.6±678.2)pmol/L]低于他莫昔芬组[(2629.2±1931.5)pmol/L]和氯米芬组[(1971.2±1222.8)pmol/L](P<0.001);3组间加用尿促性腺激素(HMG)周期数,HCG日子宫内膜厚度、血黄体生成素及孕酮、直径≥18mm成熟卵泡数,妊娠率和早期流产率,差异无统计学意义(P>0.05);HCG日子宫内膜的厚度与注射HCG的月经周期日及月经第10天的子宫内膜厚度呈正相关(P<0.05),与药物的种类及HCG日血E2水平等无显...