The luteal phase in polycystic ovary syndrome during ovulation induction with human menopausal gonadotropin with and without leuprolide acetate

Little data exist on the effects of adjunctive therapy with leuprolide acetate (LA) in the luteal phase of women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with human menopausal gonadotropin (hMG). Additionally, it is not known whether gonadal steroid concentrations in the luteal phase of induced cycles in PCOS are predictive of pregnancy. In this prospective, randomized study comparing cycles using hMG alone (n = 26) with cycles using hMG with LA (n = 33), no differences were noted between treatment groups in progesterone (P), estradiol (E2), and P:E2 ratios on luteal days 3, 6, and 9. When all treatment cycles were pooled, there were no differences in P, E2, or P:E2 ratios, comparing conception and nonconception cycles. We conclude that adjunctive therapy with LA in PCOS patients undergoing ovulation induction with hMG does not alter the luteal phase concentrations of P, E2, and P:E2. Furthermore, no correlation was found between the serum concentrations of these luteal phase steroids and cycle fecundity.     

Ovarian hyperstimulation in polycystic ovary syndrome during therapy with leuprolide acetate

Continuous exposure to GnRH eliminates the pituitary as a source of gonadotropins and may have direct suppressive effects on the ovary. A woman with PCO syndrome received leuprolide acetate (1 mg/d SC) for 4 weeks before and simultaneously with hMG stimulation. Human chorionic gonadotropin (5,000 IU) was administered IM on the 8th day of hMG therapy. There were 10 follicles greater than 15 mm and a polycystic appearance to the ovaries with 25 follicles measuring less than 10 mm. The serum E2 concentration was 2,280 pg/mL. She developed severe ovarian hyperstimulation and required hospitalization for 12 days for fluid management. A viable intrauterine pregnancy was present. Four weeks of pretreatment with leuprolide did not prevent hyperstimulation in the presence of an intrauterine pregnancy.     

Multiple consecutive cycles of ovulation induction with human menopausal gonadotropins

Human menopausal gonadotropins were administered in multiple repetitive cycles for ovulation induction. Ovarian response, as judged by peak E2 levels and the day of hCG administration, remained similar in 3-12 immediately successive cycles. We conclude that hMG can be administered in multiple successive cycles without clinically impairing ovarian response.     

Optimizing ovulation induction in women with polycystic ovary syndrome

Recent developments in our understanding of the pathophysiology of polycystic ovary syndrome led to the introduction of new therapeutic approaches. It is apparent that a significant proportion of women with polycystic ovary syndrome have insulin resistance and compensatory hyperinsulinemia. Growing evidence indicates that elevated serum insulin induces hyperandrogenism, which in turn leads to anovulation and infertility. Hyperinsulinemia also contributes to the increased risk for cardiovascular disorders and type 2 diabetes mellitus. These concepts provide rationale for therapies focused on treatments of insulin resistance. In particular, weight loss and exercise have been shown to increase insulin sensitivity and improve ovulatory function. Metformin, an insulin-sensitizing agent, is particularly effective in women with polycystic ovary syndrome who have significant insulin resistance. Metformin use leads to a decrease in serum insulin and androgen levels as well as an improvement in ovulatory function. Moreover, it appears to ameliorate cardiovascular risk factors. Other approaches to ovulation induction in women with polycystic ovary syndrome include traditional therapies using clomiphene citrate or gonadotropins. In clomiphene-resistant subjects, one can consider laparoscopic ovarian drilling and other forms of partial ovarian resection or destruction.     

Premature luteinization and ovulation induction using human menopausal gonadotrophin or pure follicle stimulating hormone in patients with polycystic ovary syndrome

High ovulation rates can be achieved in women with PCOS, using hMG or FSH to induce ovulation, but the pregnancy rate is lower than expected. To determine whether this might be due to premature luteinization, progesterone levels were measured in the follicular phase of 49 infertile women with PCOS treated with hMG or FSH. The ovulation rate was 88.6% overall and 20 patients conceived. Six pregnancies aborted within four weeks of ovulation. Premature luteinization occurred in 32% of treatment cycles, of which three resulted in conception, compared to 17 conceptions in the 68% of cycles not associated with premature luteinization (p = 0.06). Of the 17 conceptions not associated with premature luteinization, three aborted and 14 proceeded to term; all three conceptions associated with premature luteinization aborted (p = 0.01). These results indicate that premature luteinization in women with PCOS is common, and has a deleterious effect on the rate of conception, and may also be a causal factor in early pregnancy loss.     

Low-dose ovulation induction with urinary gonadotropins or recombinant follicle stimulating hormone in patients with polycystic ovary syndrome.

Patients with polycystic ovary syndrome (PCOS) are highly sensitive to gonadotropins. In recent years a number of publications have shown that chronic low-dose protocols are effective in reducing complications, in particular ovarian hyperstimulation syndrome (OHSS), especially if recombinant human follicle stimulating hormone (rhFSH) is used. The aim of the present study was to compare the efficacy and safety of rhFSH (Gonal-F, Serono) versus urinary human FSH (uhFSH) (Metrodin, Serono) in a low-dose step-up protocol for ovulation induction in clomiphene-resistent infertile PCOS patients. Twenty PCOS patients were recruited in two centers for an open randomized comparative study. A starting dose of a 75-IU ampule of rhFSH or uhFSH was used for 14 days with an increment of 37.5 IU every 7 days. Human chorionic gonadotropin (hCG) (10,000 IU, Profasi, Serono) was administered if one to three follicles achieved a diameter of > or = 16 mm. Sonographic and hormonal (serum estradiol and progesterone) monitoring of the cycles was performed. All the six pregnancies induced were in the rhFSH group, but two of them ended with miscarriage. There were no differences between the two groups concerning the number of ampules used, the stimulation days, the estradiol levels on the day of hCG administration, and the progesterone levels 7 days after hCG administration. Three patients had grade II, and one patient grade III OHSS. In conclusion, our results support the literature data that rhFSH is superior to uhFSH regarding pregnancy rates, not only in in vitro fertilization cycles, but also with a low-dose protocol in patients with PCOS.     

Ovulation induction in polycystic ovary syndrome with urinary follicle-stimulating hormone or human menopausal gonadotropin

In patients with polycystic ovarian disease (PCOD) ovulation was induced with a combination of human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or with urinary follicle-stimulating hormone (uFSH; Metrodin, Serono Laboratories, Inc., Randolph, MA) alone. hMG/hCG and uFSH resulted in comparable rates of ovulation and conception in patients with PCOD. The incidence of hyperstimulation and the potential for multiple births appeared lower with uFSH. The fact that endogenous ovulation did not occur in hMG patients who had hCG withheld or in 3 of the 11 uFSH patients who had preovulatory levels of estradiol and follicles greater than 15 mm may imply that these similarly derived gonadotropins in some instances block endogenous ovulation.     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

Ovulation induction with human menopausal gonadotropins

This review has summarized the evolution of hMG stimulation of ovulation in amenorrheic individuals, its monitoring, and its complications. Based on the principles learned from these individuals, use of hMG has now extended to women with cervical mucus deficiencies or luteal phase defects, as well as in vitro fertilization. Recommendations regarding the use of hMG at the current time when assessment by both serum E2 and ultrasound are available have been made. Briefly, it is suggested that an "E2 window" of at least 1000 pg/ml be achieved over the course of a 9- to 12-day follicular phase. Furthermore, assessment of these monitoring modalities should be made in combination in order that findings from one modality alone not be allowed to initiate premature hCG administration.     

罗格列酮用于多囊卵巢综合征促排卵治疗的效果观察

目的　探讨罗格列酮 (rosiglitazone)对存在胰岛素抵抗的多囊卵巢综合征 (polycysticovarysyndrome ,PCOS)患者促排卵治疗的效果。 方法　选择存在胰岛素抵抗的PCOS患者 96例 ,将其随机分为A、B、C组。A组 (2 8例 )口服氯米芬、B组 (3 2例 )口服罗格列酮、C组 (3 6例 )口服罗格列酮联合氯米芬 ,3组用药时间均为 3个月经周期。比较 3组用药前后的胰岛素抵抗指数的变化和排卵情况。结果　B组和C组患者治疗后 ,应用稳态模型评估的胰岛素抵抗指数 (homeostasismodelassessmentinsulinresistance ,HOMAIR)分别由 1 2± 0 6、1 1± 0 5下降为 0 6± 0 2、0 6± 0 4,两组治疗前后比较 ,差异也有显著性 (P <0 0 5)。C组治疗后排卵率为 80 % ,明显高于A组的 59%和B组的 3 5% ,差异有显著性 (P <0 0 5)。结论　罗格列酮能有效地改善胰岛素抵抗 ,提高促排卵治疗的成功率     

Human in vitro fertilization employing individualized ovulation induction by human menopausal gonadotropins

One hundred six women suffering from obstructive tubal disease not corrected by previous surgery were treated in an in vitro fertilization (IVF) program. Ovulation was induced by 3 amps of human menopausal gonadotropin (HMG)/day starting on the third day of the cycle for 5 days. In most of the patients the regmmen was continued for another 1–3 days, depending on the individual's ovarian response (means, 20±5 amps/cycle). Monitoring consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin (HCG), 10,000 IU, was administered when more than two large (1.5 to 1.8 cm in diameter) follicles were visualized. Using this regimen, a mean of five follicles per woman was aspirated, from which a mean of 3.9 over was recovered. The oocytes were pre-incuted for 8 or 24 hr. according to the morphological degree of inucification and dispersal of the oocyte-corona-cumulus complex. Following exposure to washed spermatozoa for 16 hr, a 68% fertilization rate was obtained. Oocytes were transferred into the uterus 48 hr after laparoscopy. Ninety-nine transfers (93% of the women) of 1–8 embryos (mean, 2.9/woman) were performed and resulted in 16 clinical pregnancies. No pregnancies occurred in 14 women transferred with one to three oocytes in the pronuclear stage and only one pregnancy (7.1%) was obtained in 14 women transferred with one cleaved oocyte. Over 70% of the women were transferred with two or more cleaved oocytes: in this group the pregnancyl transfer rate was 21%. Of thee pregnant women 5 of 16 (31%) aborted between 6 and 10 weeks of gestation and 1 (6%) had an ectopic pregnancy. The individualized regimen of HMG is valuable in increasing the number of fertilized oocytes and compensates with multiple-embryo transfers for the high early embryonic loss occurring in IVF.     

Risk of multiple gestation after ovulation induction in polycystic ovary syndrome

OBJECTIVE: To compare the incidence of multiple gestation following treatment with clomiphene citrate (CC), metformin (MET) or gonadotropins in polycystic ovary syndrome (PCOS) patients undergoing ovulation induction. STUDY DESIGN: This was a retrospective, cohort study performed in an academic reproductive endocrine practice. PCOS patients presenting for first-trimester ultrasound were identified and assigned to 1 of 3 groups: CC-resistant patients who conceived after use of metformin +/- CC (group A), CC-resistant patients who conceived after gonadotropins (group B) and PCOS patients who conceived with CC only (group C). Multiple pregnancy outcome data were collected by chart review and patient interview. RESULTS: One hundred one pregnancies were identified in PCOS patients who had conceived after ovulation induction (OI). The rate of multiple gestation was higher in group B (36%) than in A (0%) or C (11%). CONCLUSION: The rate of multiple births was significantly lower with MET use during OI. Because multiple gestation is associated with higher complication rates and medical costs, our data offer an additional reason for use of MET for OI in PCOS patients who fail CC.     

Ovulation induction with gonadotropins in women with polycystic ovary disease

Seventy-two infertile women with polycystic ovary disease (PCOD) and clomiphene citrate treatment failure underwent 220 human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) treatment cycles for ovulation induction over a period of 19 months. Forty-two patients ovulated but failed to conceive on clomiphene, and the remaining 30 failed to ovulate on clomiphene. Monitoring of treatment consisted of serum 17 beta-estradiol (E2) levels and ultrasonic assessment of follicular growth. Treatment was withheld whenever the E2 levels exceeded 1,500 pg/mL and/or when more than two follicles greater than or equal to 17 mm in diameter each were encountered on ultrasonography. Twenty-nine patients conceived (40.2%), and 23 delivered viable infants. Twenty-three of the 29 pregnancies were achieved in the 42 patients who ovulated on clomiphene, while only 6 pregnancies resulted in the 32 anovulatory patients on clomiphene. Six patients (20.6%) aborted in the first trimester. Multiple pregnancies consisted of only two sets of twins (6.9%). There were only two cases of mild hyperstimulation (2.7%) and no severe hyperstimulation. Because of the low occurrence of multiple pregnancies and hyperstimulation and the reasonable success rate, all PCOD patients should be started on this protocol.     

Ovarian hyperstimulation syndrome following ovulation induction with human menopausal gonadotropin

Twenty-seven anovulatory women who had episode(s) of ovarian hyperstimulation during ovulation induction with hMG were studied. Twenty-nine of the total 89 treatment cycles were complicated by ovarian hyperstimulation. Twenty-four-hour urinary estrogen concentrations 3 days prior to hCG administration were significantly higher in the hyperstimulated (H) than in the nonhyperstimulated cycles (NH). Patients who had progesterone withdrawal bleeding (Group I) were more prone to be hyperstimulated in the first treatment cycle than patients who had no progesterone withdrawal bleeding (Group II). In all instances, the syndrome resolved spontaneously with time. The pregnancy rate of H was threefold NH. It is concluded that hyperstimulation in patients who had evidence of endogenous estrogen activity as demonstrated by progesterone withdrawal bleeding tend to occur in the first treatment cycle. Strict monitoring decreased the incidence of severe hyperstimulation. A minimal amount of hyperstimulation might be beneficial to improve the pregnancy rate.     

Partial hypopituitarism and hyperprolactinemia: successful induction of ovulation with bromocriptine and human menopausal gonadotropins

The case of a patient who developed partial hypopituitarism (hypogonadotropism and growth hormone deficiency) following transphenoidal removal of a prolactinoma is described. Hypogonadotropism persisted despite restoration of normoprolactinemia with bromocriptine therapy. Successful induction of ovulation with human menopausal gonadotropin (hMG) and bromocriptine suppression of the hyperprolactinemia was carried out, resulting in a pregnancy. The pros and cons of operative and nonoperative management of hyperprolactinemia are discussed.     

Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome

Background.?The dichotomy between ovulation rates and pregnancy rates for women with polycystic ovary syndrome (PCOS) treated with clomiphene citrate (CC) prompted the present study to determine the effect of CC on endometrial maturity.

Methods.?Retrospective case–control study of anovulatory women with PCOS (n = 119) on their third ovulatory cycle of CC and controls, 238 healthy regularly ovulating women whose partners had abnormal sperm, all of whom had an endometrial biopsy in the late luteal phase.

Results.?Endometrial histology classified according to the classical Noyes criteria revealed out-of-phase endometrium in 19/119 (16%) of the CC group compared with 7/238 (3%) in controls (p < 0.0001). Duration of the luteal phase was not influenced by histological age of the endometrium. Endometrial biopsy performed during 138 conception cycles extracted from the database did not increase the miscarriage rate significantly (23.9%).

Conclusions.?CC treatment significantly increases the prevalence of out-of-phase endometrium and this could explain, in part, the large difference between ovulation and pregnancy rates. There was no correlation between the results of the endometrial biopsy and the duration of the luteal phase. Performing an endometrial biopsy during a conception cycle does not seem to have a significant negative effect on the outcome of pregnancy.     

Growth patterns of ovarian follicles during induction of ovulation with decreasing doses of human menopausal gonadotropin following presumed selection in polycystic ovary syndrome.

Data presented in this study indicate that ovulation can be induced in patients with PCOS using a GnRH analogue combined with hMG in a decreasing dose regimen. Based on the observed decline in functional, medium sized follicles in the late follicular phase, it may be speculated that the risk of ovarian hyperstimulation during gonadotropin induction of ovulation in patients with PCOS can be reduced.