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Ovarian drilling was performed by THL in all patients; no surgical complications occurred. Mean (+/-SD) duration of follow-up time was 6.3 +/- 3.3 months. Six patients recovered to have regular ovulatory cycles. Six pregnancies occurred; three were spontaneous, two occurred after stimulation and intrauterine insemination, and one occurred after IVF. The cumulative pregnancy rate was 33% at 3 months after THL and 71% at 6 months after THL. No miscarriages occurred.
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The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR) = 1.55 (95% confidence interval (CI): 1.26-1.90; I(2) = 0%) and RR = 1.38 (95% CI: 1.05-1.83; I(2) = 61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.
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A review over five years of 232 patients attending an artificial insemination by donor (AID) clinic was undertaken in order to detect abnormalities in ovulation patterns. Ovulation was determined by luteal phase progesterone estimations. Unexpected anovulation was found in 36% of the patients attending despite an apparently normal previous menstrual history and investigations. This group consisted of 22% who were anovulatory from commencement in the programme and 14% who became anovulatory during treatment. The cumulative pregnancy rates at 15 months for these two groups were lower (73% and 55%) than that for the remaining patients who ovulated normally (90%). A proportion (16%) of the latter group were receiving clomiphene therapy for anovulation recognized before entering the programme. The lower pregnancy rate could not be related to other factors influencing conception and occurred in spite of clomiphene therapy. These results should assist in advising patients on their chances of conception, preventing early discouragement but not encouraging long term insemination which may not improve the pregnancy rate.
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The YJYTT could markedly improve the clinical symptoms and pregnancy rate of PCOS patients, particularly showing good effect to the clomiphen resistant patients. The mechanism possibly was due to its regulation on hypothalamus-pituitary-ovarium axis and reducing the insulin resistance.
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COH + IUI did not improve pregnancy rates in any stage of endometriosis. In stage III/IV we recommend postoperative in vitro fertilization.
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A total of 409 sterility patients with amenorrhea classified as group II according to the WHO rating scheme were treated with a daily dose of 100 mg of Clomiphene daily for five days in 452 cycles. In addition, 300 infertile subjects with spontaneous cycles (375), but with slight irregularities in the lengths of cycles were included in this investigation as control group. Daily LH serum levels were monitored by rapid solid-phase coated tube RIA. 61.87% of LH single peaks, 28.53% of plateau peaks and 0.53% of double peaks were registered in spontaneous cycles. Similarly, 60.28% single peaks, 23.67% plateau peaks and 0.66% double peaks were registered in Clomiphene-induced cycles. Highest rate of LH plateau and single peaks were found 4 to 6 days and 5 to 7 days, resp., after the end of Clomiphene therapy. No LH peaks were found in 9.07% of spontaneous cycles and in 15.39% of Clomiphene-induced cycles. Data combine to suggest that timing of ovulation by a rapid LH radioimmunoassay is a valuable aid in consulting infertile couples. Failures of patients to conceive must be due to causes other than incorrect timing of ovulation.
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These studies are too small to clearly demonstrate clinically significant differences in pregnancy rate between the two approaches. However, data from IVF studies suggest that there may be an increased risk of OHSS associated with GnRHa use. In the absence of evidence suggesting a benefit of GnRHa augmentation for PCOS, it should not be recommended as a standard treatment for this patient group. Further studies assessing live birth and OHSS rates are warranted.
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Laparoscopic ovarian drilling (LOD) is an alternative to ovulation induction with gonadotropins for polycystic ovarian syndrome (PCOS) patients unresponsive to clomiphene. It is quick and easy to perform, although the number of punctures and energy doses has not been standardized. The mechanism of LOD is unclear, but it is likely mediated by a reduction in intraovarian androgen production. Serum luteinizing hormone and testosterone levels are rapidly normalized, and these changes are sustained over long-term follow-up. Studies have shown that ovulation and pregnancy rates are comparable between ovulation induction with gonadotropins and LOD, but LOD avoids the risks of multiple pregnancy and ovarian hyperstimulation syndrome. LOD is also more cost effective and better tolerated than gonadotropin therapy. Concerns regarding clinically significant adhesion formation and premature ovarian failure are not supported by the available data. Transvaginal hydrolaparoscopy and ultrasound guidance are less invasive techniques for performing ovarian drilling and may encourage LOD earlier in the course of treatment for PCOS.
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Pulsatile subcutaneous administration of LH-RH (14.4 micrograms/pulse/90 minutes) during the midfollicular phase (days 7 to 11) of the cycle induced significant increases in circulating LH, FSH, and E2 in all eight women treated. When CC (150 mg/day on days 2 to 6) was administered prior to the LH-RH, multiple follicular development occurred, five to seven mature follicles (greater than 16 mm) being found on day 12 of the cycle. The administration of pulsatile LH-RH in this manner may prove to be an additional regimen for use in IVF programs.
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Kaplan-Meier estimations of cumulative pregnancy rates were compared by stage between COH/IUI and spontaneous cycles. Patients with stage I/II endometriosis attempted spontaneous pregnancy for 669 months and 216 COH + IUI cycles, and patients with stage III/IV endometriosis attempted spontaneous pregnancy for 379 months and 74 COH + IUI cycles. Crude pregnancy rates were 45.7% in stage I/II and 40.5% in stage III/IV. Twelve-month cumulative pregnancy rates in stage I/II were 45% for spontaneous attempts and 42% for COH + IUI, and in stage III/IV were 20% for spontaneous attempts and 10% for COH + IUI (not significant). Cumulative pregnancy rates for COH/IUI in stage I/II were significantly higher than in stage III/IV. Monthly fecundity rates were 3.81% for stage I/II spontaneous, 4.59% for COH/IUI, 3.05% for stage III/IV spontaneous, and 1.68% for COH/IUI (not significant).
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The study included 60 anovulatory women with polycystic ovary syndrome (PCOS) who underwent OMLOD (study group) and 60 anovulatory PCOS women, in whom conventional LOD using 10-mm laparoscope under general anesthesia was performed (comparison group). Transvaginal ultrasound scan and blood sampling to measure the serum concentrations of LH, FSH, testosterone and androstenedione were performed before and after the procedure. Intraoperative and postoperative pain scores in candidate women were evaluated during the office microlaparoscopic procedure, in addition to the number of candidates who needed extra analgesia.
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NAC as a safe and well-tolerated adjuvant to CC for induction of ovulation can improve the ovulation and pregnancy rates in PCOS patients. It may also have some beneficial impacts on endometrial thickness.
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The study comprised 218 patients with clomiphene-resistant PCOS.
The percentage of morphologically normal sperm in the raw semen, as judged by strict criteria, did not affect IUI PR. Intrauterine insemination appears to be a successful treatment modality for male factor infertility, even when the percentage of morphologically normal sperm in raw semen is very low.
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Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days.
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In summary, although clomiphene alone, two combinations of clomiphene and hMG, and high dosages of hMG alone all resulted in similar degrees of enhanced follicular recruitment at the time of hCG administration, the patients in the group receiving clomiphene alone had significantly fewer follicles at the time of laparoscopy compared with those of the other three groups. Although clomiphene alone is able to produce sufficient enhanced follicular recruitment, it appears that it is necessary for gonadotropin support to be continued to prevent atresia of some of the cohort of follicles. Second, even though we achieved our best results (with respect to number of embryos replaced per patient) with the use of high-dose hMG, we believe that the ovarian hyperstimulation produced by that regimen resulted in an abnormal luteal phase which made establishment of clinical pregnancies less likely. It is certainly possible that the observed short luteal phases might be able to be corrected with supplemental hCG and/or progesterone. Similar to the results of others, our best results (that is, the highest percentage of the establishment of continuing clinical pregnancies) occurred when the regimen of follicular recruitment agents was individualized depending upon the individual patient's response with respect to size and number of follicles and peripheral E2 levels. However, the differences in pregnancy rates among groups were not statistically significant. Although the ideal regimen for enhanced follicular recruitment has probably not yet been determined, it appears that a combination of clomiphene plus concurrent and sequential hMG in individualized dosages offers the best chance for sufficient ovarian stimulation to ultimately increase the number of embryos available for uterine replacement, and at the same time minimize the disruption of the subsequent luteal phase.
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Two patients with hypergonadotropic ovarian failure were examined. Plasma levels of LH and FSH were markedly elevated to over 113 mIU/mL (Second International Reference Preparation--human menopausal gonadotropin standard), but the FSH/LH ratio was 1 or less in both women. The plasma estradiol (E2) level was 65 pg/mL in one woman before medication, and in the other increased from below 25 to 130 pg/mL after large doses of clomiphene citrate treatment. The pituitary tissues removed by transsphenoidal surgery showed hyperplasia with numerous cells immuno-histochemically positive for LH and FSH. After surgery, the elevated plasma gonadotropins decreased and plasma E2 levels increased. Human menopausal gonadotropin after clomiphene citrate treatment induced ovulation in one patient, and cyclic administration of estrogen and progesterone induced ovulation in the other. These results suggest that elevated gonadotropins may suppress ovarian function in some cases.
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Compared with the GnRH-ant protocol, the LPOS protocol may be a better regime for PORs that can increase the numbers of retrieved oocytes and transferable embryos as well as the pregnancy rate.
Psychiatric adverse effects associated with the use of clomiphene are relatively uncommon. Though case reports link mood swings to be associated with clomiphene, it is not known to be associated with a syndromal affective episode. Being a selective estrogen receptor modulator, clomiphene affects the hypothalamus-pituitary-gonadal axis and can have potential neuropsychiatric effects in vulnerable persons. Herein we report a case of clomiphene-induced manic episode in a known bipolar male patient.
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Letrozole, CC, ovulation induction, IUI, timed intercourse.
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The incidence of hypogonadism has been steadily increasing over the last few years. Exogenous testosterone has been the standard treatment for hypogonadal men, but is associated with suppression of spermatogenesis as well as other possible adverse effects. There are other medications, currently considered "off label" for androgen replenishment, that exert their effect through modulation of the hypothalamic-gonadal axis. These medications increase endogenous testosterone levels and offer a different therapeutic approach. This review will focus on these alternative (off-label) therapies for androgen replacement in men.
Results are presented of gamete intra-Fallopian transfer with cryopreserved donor semen in cases of male infertility with azoospermia or extreme oligozoospermia. The female partners had no detectable infertility problems and they had first received 10 cycles of intracervical AID without success. Forty-one GIFT cycles performed on 22 such patients gave an overall pregnancy rate of 26.8% (11/41). In 64% (9/14) of these cases, pregnancy occurred after the first GIFT attempt. From these results it is suggested that GIFT with donor semen may be a reasonable alternative after AID failure. The probable reasons for success of GIFT are discussed.
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40 women, aged 23-41 years, were treated with clomiphene citrate for functional sterility. Cytohormonal smears were then taken and the estrogenic response evaluated by the Insler scoring scale. Ovulation succeeded in 25 women and 15 showed no response. In those women who ovulated, the cytohormonal smears showed a higher level of maturity before the onset of the treatment, after which regressive changes occurred in the form of a decrease of the MV values. In the ovulatory phase, normal increases in the maturity symptoms were absent which is considered to demonstrate the low value of hormonal cytodiagnosis in the monitoring of this process during the course of clomiphene citrate administration. Statistical analysis showed no antiestrogenic effect of the clomiphene citrate on the uterine cervix. In the ovulatory phase the uterine cervix estrogenic effect achieved a high level, which provided a high level of applicability of the Insler scoring scale for an evaluation of ovulation during this treatment.
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Four women presented with strongly retarded, proliferative endometrium in the luteal phase. Of these, three presented with impaired ovarian function, high basal follicle-stimulating hormone, and high follicle-stimulating hormone levels after clomiphene stimulation on cycle day 10. In the remaining 30 women, showing an in-phase endometrium after CC stimulation, a comparison of six morphological characteristics did not reveal any significant differences between the 14 women who did become pregnant and the 16 who did not. No significant differences in endometrial thickness were observed between the groups. Significant differences were found when comparing estradiol and progesterone area under the curve during the luteal phase (P < 0.001 and P < 0.01, respectively) between those who did and those who did not become pregnant.