Inducible and endothelial nitric oxide synthase: genetic background affects ovulation in mice.

OBJECTIVE: Inducible nitric oxide synthase (NOS) and endothelial NOS are involved in female reproductive physiology. We sought to investigate the influence of the inducible (Nos2) and endothelial (Nos3) NOS genes as a function of genetic background on ovulatory capacity and early embryonic development in a mouse model. DESIGN: Observational study of genetically altered mice and their response to a superovulation protocol. SETTING: Academic research institution. ANIMALS: Wild-type mice and mice deficient for Nos2 or Nos3 were bred to C57BL/6J and 129/Sv genetic backgrounds. INTERVENTION(S): Superovulation protocol, oocyte culture. MAIN OUTCOME MEASURE(S): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology. RESULT(S): The mean number of oocytes was significantly reduced in Nos3 deficient mice on a C57BL/6J background compared with controls. Oocytes deficient for Nos3 on a C57BL/6J background also showed reduced progression to two-cell stage embryos after 24 hours, two-cell stage embryos to blastocyst stage embryos, and survival to 48 hours. Those effects were distinctly absent in mice deficient for Nos3 on a 129/Sv background and in mice deficient for Nos2 on either genetic background. CONCLUSION(S): Our data show that disruption of Nos2 had no effect on ovulation in our mice. The negative effect of Nos3 deficiency on ovulatory capacity and early embryonic development is modulated by genetic background. This suggests a role for strain-specific modifier genes in these processes.     

Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology

OBJECTIVE: To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation. Design: Prospective analysis. SETTING: University IVF program. PATIENT(s): Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12). INTERVENTION(s): Controlled ovarian hyperstimulation and IVF. MAIN OUTCOME MEASURE(s): Serum estradiol, testosterone, and leptin. RESULT(s): Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively). CONCLUSION(s): Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.     

A polymorphism of the Nos3 gene and age at natural menopause

To investigate the possible influence of a polymorphism of the Nos3 gene on menarche and onset of menopause in humans.Cohort study.Academic research institution.Ninety-one consecutive Caucasian postmenopausal women.Peripheral venous puncture and a patient questionnaire were administered.A tandem repeat polymorphism in intron 4 of Nos3 was analyzed by polymerase chain reaction amplification.The common B allele was identified on 143 of 182 chromosomes (frequency 0.79). The polymorphic A allele was present on 39 chromosomes (frequency 0.21). The genotype frequencies were as follows: 58.2% (B/B), 40.7% (A/B), and 1.1% (A/A). Age at menarche, number of deliveries, number of miscarriages, and onset of menopause did not differ between genotypes. Smoking and increased body mass index were associated with an earlier onset of natural menopause.In contrast to mouse models, in humans Nos3 does not seem to modulate onset and cessation of menses.     

Relationship of age at menarche and subsequent fertility.

We investigated retrospectively the relationship between the age at menarche and reproductive ability in 2278 married women. Those who had a pregnancy experienced menarche at a mean age (+/- SEM) of 13.7 +/- 0.1 years, and those who were infertile had menarche at a mean age of 14.0 +/- 0.2 years, difference in the times of onset of menarche being significant (P less than 0.05). Moreover, a group in whom menstruation started after the age of 18 years had a significantly higher rate of infertility (15.7%) than the others (5.0%). Irregular menstruations during the first few years after menarche was also related to decreased reproductive ability. These findings indicate the importance of menarche before the age of 18 for normal reproductive functioning.     

初潮及绝经年龄等因素与绝经后骨质疏松症发病的关系

目的探讨初潮年龄和绝经年龄、生育次数及哺乳时间与绝经后骨质疏松症发病的关系。方法1999年5月至2003年4月,对已绝经的1472例妇女进行骨密度测定,并对不同月经初潮年龄、绝经年龄、生育次数及哺乳时间妇女的骨质疏松症发生率及骨密度进行分析比较。骨质疏松症的诊断标准为骨密度值低于或等于正常年轻妇女平均骨密度峰值减去2.5个标准差。结果1472例中,共发生骨质疏松症861例,发生率为58.5%。其中绝经年限为1~10年、初潮年龄≥17岁者336例,发生骨质疏松症119例(35.4%);初潮年龄≤13岁者276例,发生骨质疏松症75例(27.2%)。1472例妇女中,初潮年龄11~13岁者,腰椎骨密度为(0.83±0.16)g/cm2;14~16岁者为(0.82±0.16)g/cm2;17~19岁者为(0.80±0.14)g/cm2;初潮年龄11~13岁者与17~19岁者比较,差异有统计学意义(P<0.05)。1472例妇女中,年龄为55~65岁、绝经年龄≤48岁者156例,发生骨质疏松症98例(62.8%);绝经年龄≥54岁者80例,发生骨质疏松症33例(41.3%),两者比较,差异有统计学意义(P<0.01)。1472例妇女中,生育次数≥4次者225例,腰椎、大转子及W ard三角区骨密度分别为(0.76±0.16)、(0.49±0.10)及(0.38±0.19)g/cm2;生育次数≤1次者475例,分别为(0.85±0.15)、(0.57±0.10)及(0.52±0.11)g/cm2,两者各部位骨密度比较,差异均有统计学意义(P<0.05)。1472例妇女中,哺乳时间≥36个月者249例,腰椎、W ard三角区骨密度分别为(0.76±0.16)及(0.40±0.10)g/m2;哺乳时间≤6个月者418例分别为(0.83±0.17)及(0.48±0.12)g/m2,两者各部位骨密度比较,差异均有统计学意义(P<0.05)。结论月经初潮时间晚及绝经时间早的妇女,骨质疏松症的发生率高;生育次数多,哺乳时间长的妇女的骨密度低于生育次数少、哺乳时间短的妇女。     

Hormonal profile and endometrial morphology in letrozole-controlled ovarian hyperstimulation in ovulatory infertile patients

OBJECTIVE: To evaluate the clinical response and endometrial morphology during the implantation window on ovarian hyperstimulation with the aromatase inhibitor letrozole in infertile ovulatory women. DESIGN: Prospective trial in infertile patients. SETTING: Tertiary care hospital. PATIENT(S): Eight ovulatory infertile patient candidates for ovarian superovulation. INTERVENTION(S): Subjects were monitored in one control cycle. In the next cycle, they received letrozole 5.0 mg daily on days 3 through 7 after menses. MAIN OUTCOME MEASURE(S): Number of ovulatory follicles; dominant follicle diameter; endometrial thickness; hormonal profile of FSH, LH, E(2), A, T, and P; endometrial histological dating; and pinopode formation assessed by scanning electron microscopy. RESULT(S): Cycles stimulated with letrozole resulted in more ovulatory follicles than did natural cycles (mean +/- SD 2.0 +/- 0.9 vs. 1.0 +/- 0.0), which attained a greater preovulatory diameter (mean +/- SD 23.8 +/- 2.7 vs. 19.3 +/- 2.1 mm), with similar endometrial thickness at midcycle compared with spontaneous cycles. Endocrine profile of medicated cycles was characterized on day 7 by increased levels of LH (5.9 +/- 0.8 vs. 3.5 +/- 0.4 IU/mL), reduced E(2) (98.4 +/- 11.4 vs. 161.5 +/- 14.7 pmol/L), and elevated androgens. Preovulatory and midsecretory E(2) were similar to spontaneous cycle, and P levels during midluteal phase were significantly elevated (44.2 +/- 4.6 vs. 27.7 +/- 4.6 pmol/L). Endometrial morphology during the implantation window in letrozole-stimulated cycles was characterized by in-phase histological dating and pinopode expression on scanning electron microscopy. CONCLUSION(S): Letrozole induces moderate ovarian hyperstimulation in ovulatory infertile patients with E(2) levels similar to spontaneous cycles and higher midluteal P, leading to both a normal endometrial histology and development of pinopodes, considered to be relevant markers of endometrial receptivity.     

In vitro fertilization for cancer patients and survivors

OBJECTIVE: To determine in vitro fertilization (IVF) outcome in cancer patients. DESIGN: Retrospective record review. SETTING: Academic, hospital-based assisted reproductive technology (ART) program. PATIENT(S): Sixty-nine women undergoing 113 IVF/gamete intrafallopian transfer (GIFT) cycles after cancer treatment in one partner, and 13 women undergoing 13 IVF cycles for embryo cryopreservation before chemotherapy/radiation. INTERVENTION(S): IVF, intracytoplasmic sperm injection (ICSI), assisted hatching, and gamete intrafallopian transfer as indicated. MAIN OUTCOME MEASURE(S): Delivery rate, spontaneous abortion rate, number of embryos cryopreserved, cancer diagnosis, systemic or local cancer treatment, female age, amount of gonadotropin used, treatment duration, peak estradiol level, and number of oocytes and embryos. RESULT(S): The women undergoing IVF after chemotherapy had poorer responses to gonadotropins than did the women with locally treated cancers even though they were younger (33.5 +/- 1.3 vs. 36.5 +/- 0.5 years; P<.05). The delivery rates after the women had undergone chemotherapy tended to be lower among the systemic treatment group than it was for the local cancer treatment group: (13.3% [2 of 15] vs. 40% [14 of 56, P=NS]). The women who had cryopreserved all embryos before chemotherapy produced more oocytes (18.7 +/- 3.2 vs. 14.5 +/- 1.2) and embryos (11.3 +/- 1.9 vs. 7.5 +/- 0.7) than did the women who had had a history of local cancer treatment. Male factor infertility as a result of cancer treatment is well treated with IVF or intracytoplasmic sperm injection, where indicated (32% delivery rate/cycle), with no difference between the frozen sperm banked before cancer treatment and fresh sperm produced after treatment. CONCLUSION(S): Chemotherapy diminishes the response to ovulation induction in assisted reproductive technologies. IVF with cryopreservation of embryos allows embryo banking before chemotherapy for women who have been newly diagnosed with cancer. Factors related to the partner affect the success of IVF for male factor infertility as a result of cancer treatment.     

Ovarian responses to menopausal gonadotropins in groups of patients with differing basal growth hormone levels.

OBJECTIVE: To investigate the relationship between endogenous serum levels of human growth hormone (hGH) and ovarian response to human menopausal gonadotropins (hMG). DESIGN: Retrospective analysis of patient response to hMG. SETTING: Center for assisted reproductive technology. PATIENTS: Eighty women who had undergone controlled ovarian hyperstimulation with hMG. Basal levels of hGH in sera from 40 of these patients were less than 5.0 microIU/mL (low hGH), values for the remaining 40 were greater than 5.0 microIU/mL (high hGH). Levels of hGH in day 2 sera were analyzed against numbers of oocytes recovered in an additional 182 patients. MAIN OUTCOME MEASURES: Serum estradiol (E2) levels and numbers of oocytes recovered at oocyte pick-up. RESULTS: Average (+/- SE) levels of hGH in sera of high-hGH and low-hGH patients were 10.2 +/- 0.6 and 2.47 +/- 0.3 microIU/mL, respectively (P less than 0.05). Respective peripheral levels of insulin-like growth factor-I were 105.3 +/- 2.9 and 97.2 +/- 2.8 ng/mL. Levels of E2 in serum of high-hGH patients exceeded respective (P less than 0.05) low-hGH values throughout folliculogenesis, and more oocytes were recovered from high-hGH patients (8.1 +/- 0.9 versus 4.7 +/- 0.5 for low-hGH patients; P less than 0.05). Serum progesterone values did not differ. Higher day 2 hGH levels were associated with higher numbers of oocytes recovered after controlled ovarian hyperstimulation. CONCLUSIONS: The present findings indicate that endogenous hGH may augment gonadotropins during follicle recruitment and during multiple folliculogenesis in women. The phase of maximum ovarian sensitivity to hGH/gonadotropin synergism and the nature of synergism remain unclear.     

Body composition and concentrations of leptin, neuropeptide Y, beta-endorphin, growth hormone, insulin-like growth factor-I and insulin at menarche in girls with constitutional delay of puberty.

AIM: Constitutional delay of puberty (CDP), a rare condition among girls, manifests as retarded sexual maturity past the 13th year of life. The clinical and endocrinological aspects of this interesting problem appear to have escaped attention in the literature. The purpose of the present study was to compare body composition and concentrations of leptin, neuropeptide Y (NPY), beta-endorphin, growth hormone (GH), insulin growth factor-I (IGF-I) and insulin at menarche in CDP girls and girls with normal pubertal development (NP). MATERIALS AND METHODS: We enrolled 11 girls with CDP and 40 girls with NP. All participants were studied at or within 3 months of menarche. Age, height and weight were recorded. Body composition was established with a body composition analyzer. Radioimmunoassays were performed to measure concentrations of NPY, beta-endorphin, leptin, GH, IGF-I and insulin. RESULTS: The mean age at menarche in the CDP and NP groups was 16.1 and 12.5 years, respectively (p = 0.0001). CDP girls at menarche were taller (1.64 vs. 1.57 m; p = 0.012). The difference between groups in body weight (57.5 vs. 50.4 kg; p = 0.1), body mass index (BMI), fat mass, fat percentage (BF%) and lean mass was not significant, and nor was the difference in leptin, GH and insulin levels. However, CDP girls demonstrated significantly higher NPY concentrations (199.4+/-105.1 vs. 56.9+/-26.3 pg/ml; p = 0.001). NPY correlated with BF% (r = 0.60) in this group. IGF-I concentrations were significantly lower in CDP girls (524.8+/-50.6 ng/ml) than in NP girls (744.5+/-56.1 ng/ml; p = 0.024). CONCLUSION: Girls with CDP differed from NP girls only in age at menarche and height; they did not differ significantly with respect to BMI and body composition parameters. Higher concentrations of NPY in CDP girls may be responsible for CDP and reduced levels of IGF-I. Correlation of NPY with BF% suggests an involvement of this neuropeptide in the process of fat accumulation associated with CDP.     

Reproductive aging is associated with decreased mitochondrial abundance and altered structure in murine oocytes

Purpose

To establish the phenotype of reproductive aging in our mouse model. To test the hypotheses that reproductive aging is associated with a decrease in mitochondrial abundance that could ultimately reflect dysfunction in oocytes.

Methods

Breeding studies were performed in young and aged female virgin wild type C57BL6J mice to establish their reproductive phenotype by measuring time to conception, litter size, and live birth per dam. Individual oocytes were analyzed for mtDNA content. Transmission electron microscopy was used to study ultrastructure of mitochondria in oocytes.

Results

Old females were found to have significantly prolonged time to conception and fewer surviving pups in their litters. Oocytes from old mice had 2.7-fold less mtDNA compared to younger controls (p < 0.001; 95 % CI 2.1–3.5). Decrease in mitochondrial organelle abundance in old animal’s oocytes was confirmed with transmission electron microscopy. Distinct morphological changes were noted in mitochondria, suggesting altered mitochondrial biogenesis in the old animals’ oocytes.

Conclusions

Reproductive aging in mice is associated with reduced reproductive competence. Aging is associated with a significant decrease in number of mitochondria in oocytes. Our data support mitochondrial organelle loss and dysfunction in oocytes as a potential etiology for reproductive senescence.     

Reproductive period and cognitive function in a representative sample of naturally postmenopausal women aged 60-64 years.

BACKGROUND: Greater lifetime estrogen exposure has been postulated to result in better cognition in later life, particularly in the area of verbal memory. In women, the highest levels of endogenous estrogen occur during their reproductive period, between menarche and menopause. OBJECTIVE: To investigate the association between reproductive period and cognition. METHODS: The sample consisted of 760 naturally postmenopausal women aged 60-64 years (mean age 62.5 +/- 1.5 years) participating in the PATH Through Life Study who were randomly drawn from the population of Canberra, Australia. Participants were administered a verbal learning test (immediate recall and 1-minute delay), the Mini-Mental State Examination (MMSE), digit span backwards, the Symbol-Digit Modalities Test and simple and choice reaction time tests. RESULTS: There were no significant associations detected between reproductive period and performance on any of the cognitive tests, either before or after controlling for potential confounding variables. CONCLUSIONS: Reproductive period, a surrogate measure of endogenous estrogen exposure, had no detectable effect on cognitive performance in this sample.     

Platelet activation status decreases after menopause.

OBJECTIVE: The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation. BACKGROUND: Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women. METHODS: By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb-IIIa complex (GPIIb-IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets x mean fluorescence of positive platelets). Also, thromboxane A2 was quantified by means of its main plasma metabolite, thromboxane B2, by enzyme immunoassay. RESULTS: P-selectin and GPIIb-IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin+ platelets and of GPIIb-IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3 +/- 3, n = 10) and Group B (6.2 +/- 2.9, n = 27; mean +/- standard deviation (SD), p < 0.001). GPIIb-IIIa binding index also differed significantly between both groups (Group A: 18.8 +/- 2.3, n = 10 vs. Group B: 16.2 +/- 3.1, n = 27; mean +/- SD, p < 0.0018). Plasma concentration of thromboxane B2 was 1.07 +/- 0.5 pg/well before menopause (Group A, n = 10) and 1.9 +/- 4.1 pg/well after menopause (Group B, n = 27), not significantly different (mean +/- SD, baseline x therapy, p = 0.85). CONCLUSIONS: After the menopause, climacteric women--whose estradiol status is low--have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.     

Influence of the angiotensinogen gene on the ovulatory capacity of mice

Objective: The tissue-bound ovarian renin-angiotensin system (OVRAS) is critically involved in ovulation in humans and rodents. Mice with disruption and overexpression of the angiotensinogen gene (Agt) have been previously generated. We investigated the influence of varying Agt gene expression on the ovulatory capacity and early embryonic development in mice.

Design: Observational study of genetically altered mice and their response to a superovulation protocol.

Setting: Academic research institution.

Animal(s): Mice with varying copy numbers of Agt (one copy: N = 48; two copies: N = 51; three copies: N = 20; four copies: N = 24).

Intervention(s): Superovulation protocol, oocyte culture.

Main Outcome Measure(s): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology, serum estradiol measurements.

Result(s): The mean number of oocytes harvested was greatest in wild-type mice (two copies of Agt, 39.9 ± 14) with a reduction of ovulatory capacity in mice overexpressing Agt (three copies [34.8 ± 11.7] and four copies [31.2 ± 12.4], P = .026). Mice with one copy of Agt showed a slight decrease of ovulatory capacity compared to wild-type mice (35.8 ± 15.2, P = .29). Ovarian histology, serum estradiol levels, and early embryonic development were independent of the Agt genotype.

Conclusion(s): Overexpression of Agt was associated with reduced ovulatory capacity, but with none of the other parameters that were evaluated. These findings support an important role of the ovarian renin-angiotensin system in the process of follicular rupture.     

Gynecological factors and body mass index as determinants of bone mass in normal postmenopausal women. A study with peripheral quantitative computed tomography (pQCT)

OBJECTIVE: This paper studied the influence of several gynecological factors (years since menopause (YSM), age at menarche and gynecological age or reproductive life) simultaneously with anthropometric factors as determinants of bone mass in 189 healthy postmenopausal women. METHODS: Bone mass was determined by peripheral quantitative computed tomography. RESULTS: An overall evaluation showed that YSM correlated negatively with trabecular and cortical bone density (BMDTrab and BMDCorti) (P<0.05 in both cases). Age at menarche correlated negatively with BMDCorti (P<0.05) and gynecological age correlated positively with BMDTrab (P<0.05). Classifying the women according to their body mass index (BMI), the YSM correlation persisted in those subjects whose BMI was >25 kg/m(2), and in age at menarche and gynecological age of women whose BMI was <25 kg/m(2) (P<0.05). After separating women according to their age at menarche, their gynecological age and BMI, the only significant difference that persisted was in BMDTrab which was lower in the group with gynecological age <33 years, with a BMI <25 kg/m(2) (P=0.020). Parity and smoking had no impact on our results. By multiple regression, with BMD as the dependent variable and the gynecological factors as independent variables, we only observed significance between YSM and BMDCorti (P<0.005). The same was observed after separating women according to their BMI in the >25 kg/m(2) group (P<0.05). CONCLUSIONS: Our data stress the importance of YSM on BMDTrab and BMDCorti, of age at menarche on BMDCorti and of gynecological age on BMDTrab. However, YSM is the gynecological factor that mainly determines BMD. The differences observed between measurements taken with pQCT and other methods commonly used to estimate bone mass indicate that results obtained with one technique cannot be extrapolated to other methods.     

Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin

The purpose of this study was to analyze follicular fluid (FF) samples for steroid levels from stimulated and unstimulated cycles triggered with human chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous ovulatory cycles were monitored with serial ultrasound examinations, and hCG 10,000 IU was given when the lead follicle was mature. Fourteen FF samples yielding fertilizable oocytes were compared with 13 FF samples from controlled ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is associated with increased FF P, decreased FF E2, T, and A levels, and decreased T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase activity.     

Menstrual blood loss measured 5-6 years after endometrial ablation

OBJECTIVE: To examine objectively the long-term efficacy of endometrial ablation for menorrhagia. METHODS: Thirty-nine women with menorrhagia due to ovulatory dysfunctional bleeding treated previously by rollerball ablation were followed up 5-6 years later. Menstrual blood in sanitary towels was measured with the alkaline hematin technique in 26 women who were still premenopausal and in whom menstrual blood loss had been measured before and immediately after the original ablation. RESULTS: Mean (+/- standard deviation [SD]) menstrual blood loss (per menstrual period) was reduced from 90 mL +/- 14.4 before ablation to 3.8 mL +/- 2.1 at 3 months, 1.8 mL +/- 1.0 at 6 months, and 3.3 mL +/- 1.3 at 5-6 years after ablation. In women who were still menstruating, the mean hemoglobin concentration rose significantly from 126 to 135 g/L (P = .022). CONCLUSION: Rollerball endometrial ablation is a highly effective long-term therapy for carefully selected women with menorrhagia due to ovulatory dysfunctional uterine bleeding.     

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

OBJECTIVE: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). DESIGN: Retrospective data analysis of selective groups of patients. SETTING: A private IVF unit. PATIENT(S): Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. INTERVENTION(S): In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. MAIN OUTCOME MEASURE(S): Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle's E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). RESULT(S): In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S): Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.     

A low number of retrieved oocytes at in vitro fertilization treatment is predictive of early menopause

OBJECTIVE: To investigate whether women with a low number of retrieved oocytes at the first in vitro fertilization (IVF) attempt have an increased risk of early menopause. DESIGN: Nested case-control study. SETTING: Twelve IVF clinics in the Netherlands. PATIENT(S): Women participating in a nationwide Dutch cohort study (OMEGA) of ovarian stimulation for IVF and subsequent gynecologic diseases (n = 26,428). Each patient who experienced natural menopause at or before 46 years (n = 38) was individually matched to five controls (n = 190) who had not yet entered menopause at the age the patient became postmenopausal.INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative risk of reaching natural menopause at an early age ( three oocytes). Women who were stimulated with gonadotropins during IVF treatment but did not undergo an IVF puncture because of an anticipated poor response (canceled IVF cycle) had a relative risk of 8.3 (95% confidence interval: 2.9-23.9). CONCLUSION: These results suggest that women with a low number of retrieved oocytes at the first IVF treatment are more likely to become postmenopausal at an early age than women with a higher number of retrieved oocytes. Our study is the first longitudinal study to provide strong evidence for the quantitative aspect of the ovarian concept of reproductive aging.     

Cigarette smoking damages women's reproductive life

Female smokers experienced menopause significantly (P 相似文献   

Urinary reproductive hormone level differences between African American and Caucasian women of reproductive age

OBJECTIVE: To compare urinary levels of reproductive hormones in African American and Caucasian women. DESIGN: Cross-sectional study. SETTING: Ten United States Air Force (USAF) bases. PATIENT(S): African American (n = 33) and Caucasian (n = 65) women of reproductive age from a larger study of USAF women (n = 170). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary endocrine end points: follicular luteinizing hormone (LH), preovulatory LH, level of LH surge peak, early follicular follicle stimulating hormone (FSH), follicular LH:FSH ratio, midluteal FSH, FSH rise before menses, early follicular estrone 3-glucuronide (E(1)3G), midfollicular E(1)3G, periovulatory E(1)3G peak, midluteal E(1)3G, early follicular pregnanediol 3-glucuronide (Pd3G), follicular Pd3G, rate of periovulatory Pd3G increase, E(1)3G:Pd3G on the day of luteal transition, slope of E(1)3G:Pd3G, and midluteal Pd3G. RESULT(S): Relative to Caucasians, African American women had significantly lower follicular phase LH:FSH ratios (mean +/- SD: 0.7 +/- 0.4 vs. 1.0 +/- 0.6), lower follicular phase Pd3G levels (1.0 +/- 0.5 vs. 1.2 +/- 0.8 microg/mg creatinine), and lower rates of periovulatory Pd3G increase (0.5 +/- 0.7 vs. 1.0 +/- 1.2 microg/mg creatinine). CONCLUSION(S): Findings of this analysis should be considered preliminary evidence of racial differences in hormone levels. Future studies are needed to determine whether these differences have clinical significance.