Endometrial oestrogen and progesterone receptors and their relationship to sonographic appearance of the endometrium.
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The rapid development of ultrasonographic equipment now permits instantaneous assessment of follicles and endometrium. The sonographic appearance of the endometrium has been discussed in relation to in-vitro fertilization (IVF) cycles. However, a generally agreed view of the relationship of the sonographic appearance to fecundity in IVF cycles has not emerged. We have studied the relationship between steroid receptors and the sonographic appearance of the preovulatory endometrium in natural cycles and ovulation induction cycles. Preovulatory endometrial thickness was not found to be indicative of fecundity, although a preovulatory endometrial thickness of <9 mm related to an elevated miscarriage rate. The preovulatory endometrial echo pattern did not predict fecundity. No relationships were found among endometrial appearance, endometrial steroid receptors and steroid hormone concentrations in serum. Oestrogen or progesterone receptor concentrations were not related to endometrial thickness or to concentrations of serum oestradiol, the only significant correlation being found between the endometrial concentrations of oestrogen and progesterone receptors. The ratio of progesterone:oestrogen receptor concentration was somewhat less in echo pattern B (not triple line) endometrium compared with pattern A (triple line) endometrium. Oestrogen and progesterone receptor concentrations appeared stable on gonadotrophin induction, though fewer numbers were found during clomiphene cycles than in natural cycles. With regard to the distribution of receptor concentration between clomiphene and natural cycles, most women using clomiphene had very low oestrogen receptor populations. Pregnancy rates were low, in spite of high ovulatory rates during clomiphene treatment and were mainly related to low oestrogen receptor concentrations in preovulatory endometrium. (+info)
Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin.
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Uterine peristalsis, directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Chlomiphene tended, though insignificantly so, to suppress the frequency of peristaltic waves in the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system. (+info)
Endometrial evaluation is not predictive for in vitro fertilization treatment.
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PURPOSE: The main purpose of this study was to evaluate ovarian function by clomiphene citrate (CC) challenge test in a group of tubal infertile women and to study endometrial morphological maturation in the early luteal phase of CC-stimulated cycles as compared to in vitro fertilization (IVF) treatment outcome. METHODS AND RESULTS: 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. CONCLUSIONS: Luteal endometrium morphology was not a sharp instrument to detect differences between women who did and women who did not become pregnant following IVF treatment, while ovarian function, as measured by hormonal markers, seemed to be a more reliable prognostic factor for IVF treatment outcome. (+info)
Effects of clomiphene citrate and progesterone on resting and proliferative cell-populations in resting and proliferative cell-populations in mouse uterine epithelium.
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Resting cells (GO cells) of the uterine surface epithelium in castrated mice began to synthesize DNA with high synchrony from 10 hr after the injection of 50 ng of estradiol-17beta with or without 5.5 mug of clomiphene citrate. Highly synchronized DNA synthesis in GO cells elicited with estradiol was delayed approximately 5 hr when the simultaneous administration of 0.5 mg of progesterone was given. In GO cells of castrated mice which received 5.5 mug of clomiphene or 55 mug of clomiphene plus 50 ng of estradiol, DNA synthesis with partial synchrony began 15 hr after the injection. The effects of estradiol were completely suppressed by the administration of 55 mug of clomiphene. It is suggested that the inhibitory action of clomiphene may be due to the competitive blocking of estrogen binding, while progesterone suppresses the estrogen-induced DNA synthesis of the surface epithelium and transfers them to the GO cell-compartment. (+info)
Intrauterine insemination treatment in subfertility: an analysis of factors affecting outcome.
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A total of 811 intrauterine insemination (IUI) cycles in which clomiphene citrate/human menopausal gonadotrophin (HMG) was used for ovarian stimulation were analysed retrospectively to identify prognostic factors regarding treatment outcome. The overall pregnancy rate was 12.6% per cycle, the multiple pregnancy rate 13.7%, and the miscarriage rate 23.5%. Logistic regression analysis revealed five predictive variables as regards pregnancy: number of the treatment cycle (P = 0.009), duration of infertility (P = 0.017), age (P = 0.028), number of follicles (P = 0.031) and infertility aetiology (P = 0.045). The odds ratios for age < 40 years, unexplained infertility aetiology (versus endometriosis) and duration of infertility < or = 6 years were 3.24, 2.79 and 2.33, respectively. A multifollicular ovarian response to clomiphene citrate/HMG resulted in better treatment success than a monofollicular response, and 97% of the pregnancies were obtained in the first four treatment cycles. The results indicate that clomiphene citrate/HMG/IUI is a useful and cost-effective treatment option in women < 40 years of age with infertility duration < or = 6 years, who do not suffer from endometriosis. (+info)
Anovulations in an ovary during two menstrual cycles enhance the pregnancy potential of oocytes matured in that ovary during the following third cycle.
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The aim of this study was to test whether ovulation from an ovary affects the health of oocytes from dominant follicles in that ovary two cycles later. A total of 80 women each with two intact ovaries underwent 270 treatment cycles (155 natural cycles and 115 clomiphene citrate cycles) all showing unilateral ovulation. The results from the in-vitro fertilization (IVF) treatment were grouped according to whether ovulation (O) or anovulation (A) (no ovulation) was observed in the ovary with dominant follicle during the treatment cycle in the previous two cycles: O-O, A-O, O-A and A-A (previous second cycle-previous first cycle). The rate of pre-embryo formation in A-A was significantly higher than that of O-A. The pregnancy rate in A-A (29%) was also higher than those of O-A (13%), A-O (9%) and O-O (5%). These rates increased from O-O to A-A as the number of previous ovulations in an ovary decreased. The presence of a corpus luteum and/or a dominant follicle is likely to exert local negative effects on the health of the oocyte contained in the follicle selected to ovulate up to two cycles later. Anovulations in an ovary for two menstrual cycles may therefore provide improved conditions for the development of a healthier oocyte with an increased pregnancy potential. (+info)
The effect of smoking on oocyte quality and hormonal parameters of patients undergoing in vitro fertilization-embryo transfer.
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PURPOSE: The aim of the present study was to investigate the influence of smoking on different parameters such as oocyte count, embryo score, and basal hormone values within the scope of in vitro fertilization-embryo transfer (IVF-ET). METHODS: Eight hundred thirty-four women undergoing IVF-ET treatment were classified as smokers or nonsmokers on the basis of questionnaires. Additionally, we divided them into three groups according to their stimulation protocol--"combined stimulation" [I; clomiphene citrate plus human menopausal gonadotropin (hMG)], "ultrashort" [II; gonadotropin releasing hormone agonist (GnRHa) plus hMG or follicle-stimulating hormone (FSH)], and "long downregulation protocol" (III)--and further classified again as smokers or nonsmokers within the groups. RESULTS: In general, smoking patients were significantly (P = 0.0195) younger than nonsmokers and showed a significantly (P = 0.0379) lower embryo score and a tendency (P = 0.0931) to produce fewer oocytes. There was no significant difference concerning the number of normally or pathologically fertilized and transferred oocytes and embryos suitable for cryopreservation. Women who smoked had significantly (P = 0.0112) higher basal 17-beta-estradiol (E2), luteinizing hormone (LH) (P = 0.0001), and dehydroepian-drosteronesulfate (DHEAS) (P = 0.0039) levels, but their basal human prolactin (HPRL) levels were significantly (P = 0.0033) lower than those of nonsmokers. According to the stimulation protocol used, we found the following results. Smoking patients in group I showed a significantly (P = 0.023) lower embryo score and produced fewer oocytes (P = 0.0113), with fewer of them being fertilized (P = 0.0072) and transferred (P = 0.0067). Women who smoked had significantly (P = 0.0002) higher basal LH levels, but their HPRL levels were significantly (P = 0.031) lower than those of nonsmokers. Furthermore, they had a thinner endometrium on the day of embryo transfer (P = 0.0366). In group II we measured significantly elevated basal E2 levels (P = 0.0089) and higher LH values (P = 0.0092) in smokers. Group III showed a trend (P = 0.0565) toward lower HPRL values in smokers. CONCLUSIONS: Although the fertilization rate of oocytes and the pregnancy rate were not significantly different between smokers and nonsmokers, we found significantly alterated hormonal parameters and negatively influenced oocyte parameters, particularly after clomiphene stimulation. So we might consider using only GnRHa protocols for smoking patients. Additionally, we advise our patients to stop smoking before an IVF-ET treatment because of the complex effects of smoking on the reproductive and hormonal system. (+info)
Hormone and fertility drug use and the risk of neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group.
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Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration. (+info)