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BACKGROUND An inverse association between BMI and endometriosis has been reported but remains controversial. We decided to evaluate the association between BMI and the different types of endometriosis, classified as superficial endometriosis (SUP), deep infiltrating endometriosis (DIE) and ovarian endometrioma (OMA). METHODS From a prospective database of patients who underwent gynecological surgery between February 2005 and October 2008, we compared 238 patients with a histological diagnosis of endometriosis to 238 age- and smoking-status-matched controls using a prospective preoperative questionnaire and surgical data. Numerical variables means were compared for matched pairs, and non-parametric variables using Wilcoxon test. The Odds ratios for all types of endometriosis adjusted for confounding variables were computed according to predefined BMI groups [1(<18.5), 2 (≥18.5 and <22), 3(≥22 and <25), 4(≥25)], taking Group 3 as the reference population. RESULTS BMI was significantly lower for all 238 patients (21.70 ± 3.7 versus 23.29 ± 4.1, P < 0.001), for 101 OMA patients (21.88 ± 3.8 versus 22.99 ± 4, P < 0.038), and for 97 DIE patients (21.35 ± 3.4 versus 23.35 ± 3.8, P < 0.001) compared with their own controls, but not for the 40 SUP patients. Patients in Group 1 had adjusted odds ratios as high as 3.3 [95% confidence interval (CI): 1.6–6.8] for DIE and 2.7 (95% CI: 1.1–6.8) for OMA; in Group 2, the adjusted oddd ratios were 2.6 (95% CI: 1.3–5.5) for DIE and 2.9 (95% CI: 1.5–5.4) for OMA. CONCLUSIONS Endometriotic patients have lower BMI than age- and smoking-status-matched controls, independent of confounding variables. Patients with the lowest BMI (<18.5) are at a high risk of DIE. [ABSTRACT FROM AUTHOR]

The article offers information on the management of infertility and pelvic pain as caused by endometriosis. It states that surgery may improve the chances of conceiving from 12 to 18 months following surgery. It says that endometrioma surgery can help in reducing ovarian responses to controlled ovarian stimulation (COS). It mentions that pre-assisted reproductive technologies (ART) treatment with oral contraceptives (OC) may have a positive ART outcome in ovarian endometriosis.

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types. [ABSTRACT FROM AUTHOR]

Compliance with hormone replacement therapy (HRT) is notoriously low despite ample documentation of clinical efficacy. The two major reasons given by women who discontinue HRT are uterine bleeding and side-effects. The recent development of a controlled and sustained vaginal progesterone gel allowed single daily application and made prolonged use such as for menopause possible. Here we report our clinical experience with two therapeutic options for HRT using natural progesterone administered vaginally. A first group of 69 menopausal women received the sustained release vaginal progesterone gel, Crinone® 4% (45 mg daily) from days 1–10 of each calendar month with oestrogens taken continuously. A second group of 67 women received Crinone 4% twice weekly in conjunction with continuous oestrogen therapy. Endometrial thickness was evaluated before and after 6 months of treatment. Histological verification was obtained in all cases of abnormal bleeding. At 6 months, 63 out of 69 (91.9%) women receiving progesterone cyclically experienced predictable withdrawal bleeding. The vast majority, 54 (80.6%) of 67 women receiving Crinone in constant combined association with oestrogen therapy, remained amenorrhoeic throughout 6 months of therapy. All cases of abnormal bleeding were biopsied and no hyperplasia was seen. Our results indicate that both regimens using the sustained release vaginal progesterone gel controlled bleeding in HRT. Combined with the lower incidence of side-effects characteristic of vaginal progesterone, both vaginal progesterone regimens have the potential of improving HRT compliance. [ABSTRACT FROM PUBLISHER]

The results of many recent experimental and clinical studies support the hypothesis that progesterone administered vaginally is distributed selectively to the uterus where tissue concentrations and effects exceed expectations. This phenomenon has multiple clinical implications in several fields of gynaecological endocrinology, notably in assisted reproductive treatments and new forms of hormone replacement therapy. Yet, the actual mechanisms by which vaginal administration of progesterone can induce higher concentrations in the uterus, despite low concentrations in the systemic circulation, remain obscure and most puzzling to many gynaecologists. This review aims to muster ideas and propose different mechanisms to explain the observed phenomenon. In particular, we will summarize data that support the various putative modes of transport including, direct diffusion through tissue, intracervical aspiration, absorption into the venous or lymphatic circulatory systems and countercurrent vascular exchange with diffusion from utero-vaginal veins/lymph vessels to arteries. All these mechanisms may concur to various extents to the uterine specificity of vaginal progesterone. [ABSTRACT FROM AUTHOR]

The results of many recent experimental and clinical studies support the hypothesis that progesterone administered vaginally is distributed selectively to the uterus where tissue concentrations and effects exceed expectations. This phenomenon has multiple clinical implications in several fields of gynaecological endocrinology, notably in assisted reproductive treatments and new forms of hormone replacement therapy. Yet, the actual mechanisms by which vaginal administration of progesterone can induce higher concentrations in the uterus, despite low concentrations in the systemic circulation, remain obscure and most puzzling to many gynaecologists. This review aims to muster ideas and propose different mechanisms to explain the observed phenomenon. In particular, we will summarize data that support the various putative modes of transport including, direct diffusion through tissue, intracervical aspiration, absorption into the venous or lymphatic circulatory systems and countercurrent vascular exchange with diffusion from utero-vaginal veins/lymph vessels to arteries. All these mechanisms may concur to various extents to the uterine specificity of vaginal progesterone. [ABSTRACT FROM PUBLISHER]

To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were age < or = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency: < or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and > 5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P < 0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P < 0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone. [ABSTRACT FROM AUTHOR]

We have previously observed that exogenous oestradiol can delay the intercycle increase in plasma follicle stimulating hormone (FSH). The increase in plasma FSH that follows discontinuation of exogenous oestradiol peaks after 3 days. We have now studied the possibility of using exogenous oestradiol to synchronize the increase in endogenous FSH with the onset of human menopausal gonadotrophin (HMG) treatment in controlled ovarian hyperstimulation (COH). A total of 30 women aged 35.1 ± 6.3 years (mean ± SD) undergoing ovarian stimulation received 2 mg of oestradiol valerate twice daily starting on day 25 of the previous menstrual cycle until the first Tuesday following menses. Ovarian stimulation was initiated 3 days later. On the last day of oestradiol treatment, plasma oestradiol, FSH and luteinizing hormone (LH) (mean ± SEM) were 566 ± 53 (pmol/l), 3.8 ± 0.4 (IU/l) and 5.5 ± 0.8 (IU/l) respectively. After 3 days, the FSH and LH (mean ± SEM) had increased to 6.7 ± 0.7 and 6.9 ± 0.7 (IU/l) respectively while oestradiol decreased to 251 ± 29 (pmol/l). The mean number (± SEM) of HMG ampoules used was 25.1 ± 2.7 and treatment lasted 11.3 ± 0.9 days). Five women became pregnant for a pregnancy rate (ongoing) of 19 (15%). If all women aged >40 years (six women who did not become pregnant) were excluded from analysis the pregnancy rate (ongoing) was 24 (19%). These results indicate that exogenous oestradiol can safely be used for the synchronization of endogenous and exogenous FSH stimuli in COH. This approach provides the practical advantage of permitting an advanced timing of the onset of COH treatments when gonadotrophin-releasing hormone (GnRH) agonists are not used, which improves treatment convenience for patients and team members alike. Further development of this model may enable control of the onset of natural cycles which may find practical applications for timing assisted reproductive techniques (intrauterine insemination or in-vitro fertilization) in the natural cycle. [ABSTRACT FROM PUBLISHER]

The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects. [ABSTRACT FROM PUBLISHER]

The transfer of blastocysts obtained by co-culture with 'Vero' (African green monkey kidney) cells was offered to infertile couples with the following indications: (i) repeated failure of implantation, (ii) patients in whom multiple pregnancies had to be avoided (malformed uterus or risk of descending uterus), (iii) patients where embryo development potential had to be assessed, and (iv) replacement of supernumerary embryos frozen at the blastocyst stage. In the 142 cycles analysed, the pregnancy rates per transfer were 37.2, 36.3, 13.0 and 13.6% respectively for the couples with indications i-iv. The respective implantation rates per blastocyst were 20.0, 16.7, 7.1 and 9.3%. In patients in whom multiple pregnancies had to be avoided, the transfer of a maximum of two blastocysts gave a pregnancy rate per cycle of 23.5%, without any multiple pregnancies. The freezing of supernumerary embryos at the blastocyst stage allowed us to replace them using simple protocols and to avoid cancellation of the transfer cycles. Embryo co-culture has been found to be an interesting technique for selected indications, making available a good number of blastocysts for transfer. The transfer of blastocysts allowed us to reduce the number of embryos transferred per patient and therefore also reduce the rate of multiple pregnancies (there were no triplet pregnancies in this study). These results need to be confirmed by larger, randomized studies with comparisons to control groups to evaluate the effectiveness of blastocyst transfers. [ABSTRACT FROM AUTHOR]

The transfer of blastocysts obtained by co–culture with ‘Vero’ (African green monkey kidney) cells was offered to infertile couples with the following indications: (i) repeated failure of implantation, (ii) patients in whom multiple pregnancies had to be avoided (malformed uterus or risk of descending uterus), (iii) patients where embryo development potential had to be assessed, and (iv) replacement of supernumerary embryos frozen at the blastocyst stage. In the 142 cycles analysed, the pregnancy rates per transfer were 37.2, 36.3, 13.0 and 13.6% respectively for the couples with indications i-iv. The respective implantation rates per blastocyst were 20.0, 16.7, 7.1 and 9.3%. In patients in whom multiple pregnancies had to be avoided, the transfer of a maximum of two blastocysts gave a pregnancy rate per cycle of 23.5% without any multiple pregnancies. The freezing of supernumerary embryos at the blastocyst stage allowed us to replace them using simple protocols and to avoid cancellation of the transfer cycles. Embryo co-culture has been found to be an interesting technique for selected indications, making available a good number of blastocysts for transfer. The transfer of blastocysts allowed us to reduce the number of embryos transferred per patient and therefore also reduce the rate of multiple pregnancies (there were no triplet pregnancies in this study). These results need to be confirmed by larger, randomized studies with comparisons to control groups to evaluate the effectiveness of blastocyst transfers. [ABSTRACT FROM PUBLISHER]

Predicting ovarian response to stimulation constitutes a pivotal task in the organization of a successful in-vitro fertilization (IVF) programme. The purpose of the current study was to determine whether a new ovarian reserve test, the exogenous follicle stimulating hormone ovarian reserve test (EFORT), could improve the predictive value of the classical follicle stimulating hormone (FSH) measurements on cycle day 3 of ovarian stimulation regarding results of IVF. In this prospective study, 52 IVF candidates aged 27-42 years underwent 52 consecutive IVF cycles. These women received 300 IU of purified FSH i.m. on cycle day 3. Blood samples were taken just before the injection to measure plasma FSH and oestradiol; 24 h later, plasma oestradiol concentration was determined. Two menstrual cycles later, ovarian stimulation was performed for IVF using a time-release gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG). For the interpretation of the EFORT results, we considered the post-FSH plasma oestradiol increment (delta E2) and the baseline plasma FSH values (bFSH). The results of these two parameters were compared with the subsequent quality of the ovarian response to stimulation for IVF and the pregnancy outcome. Our results indicated a statistically significant improvement of the predictive value of the bFSH on the ovarian stimulation outcome when the EFORT parameters (bFSH and delta E2) were analysed synergistically.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

High endometrial receptivity has been achieved with physiological oestradiol and progesterone replacement cycles in women with ovarian failure. To understand whether different protocols using the oral route or the transdermal route can influence the endometrial maturation and the regulation of sex steroid receptors, we studied 33 women with ovarian failure treated by two commonly used protocols and assessed endometrial receptivity using light microscopy, scanning electron microscopy and immunohistochemistry for oestrogen and progesterone receptors on biopsies taken to include different periods of the luteal phase. The morphology in these patients was similar to that observed in women with normal ovulatory cycles, indicating that the morphological response is not dependent on the type of oestradiol, oral or transdermal, in the replacement cycles as compared to the endogenous oestradiol in the menstrual cycle. The relative distribution of steroid receptors between the epithelium and stroma varies similarly to that observed during the luteal phase of the menstrual cycle. These results confirm the role of progesterone, especially the importance of the number of days of exposure to it, in the disappearance of steroid receptors from endometrial glands. These observations give a better understanding of endometrial receptivity around the time of presumed implantation and confirm clinical results concerning the best timing of oocyte transfer. [ABSTRACT FROM AUTHOR]

High endometrial receptivity has been achieved with physiological oestradiol and progesterone replacement cycles in women with ovarian failure. To understand whether different protocols using the oral route or the transdermal route can influence the endometrial maturation and the regulation of sex steroid receptors, we studied 33 women with ovarian failure treated by two commonly used protocols and assessed endometrial receptivity using light microscopy, scanning electron microscopy and immunohistochemistry for oestrogen and progesterone receptors on biopsies taken to include different periods of the luteal phase. The morphology in these patients was similar to that observed in women with normal ovulatory cycles, indicating that the morphological response is not dependent on the type of oestradiol, oral or transdermal, in the replacement cycles as compared to the endogenous oestradiol in the menstrual cycle. The relative distribution of steroid receptors between the epithelium and stroma varies similarly to that observed during the luteal phase of the menstrual cycle. These results confirm the role of progesterone, especially the importance of the number of days of exposure to it, in the disappearance of steroid receptors from endometrial glands. These observations give a better understanding of endometrial receptivity around the time of presumed implantation and confirm clinical results concerning the best timing of oocyte transfer. [ABSTRACT FROM PUBLISHER]

Six patients with interstitial pregnancies were treated with systemic or local injections of methotrexate, 15 mg i.m. daily for 5 days, or 1 mg/kg for 1 day. One dose of folinic acid rescue (50 mg) was administered on the first day of the treatment course. Diagnosis of interstitial pregnancy was established either by laparoscopy or transvaginal ultrasound. Out of six patients, five had serial measurements of serum human chorionic gonadotrophin (HCG), progesterone (P) and 17β-oestradiol (E) until either the ectopic pregnancy resolved or surgery was performed. For one patient operated on day 1 after medical treatment, no serial serum measurements were performed. Serum HCG became undetectable under medical treatment in only four of the six patients. Out of these four patients, three had an initial level of HCG <1000 mIU/ml. Two patients underwent surgery (salpingectomy) because either the level of serum HCG did not decrease after the course of methotrexate therapy or it was required the next day to stop haemorrhage. In these patients, the initial level of HCG at the time of diagnosis, was 5300 and 43 000 mJU/ml, respectively. In the four patients who received conservative medical treatment only, the next menstrual period occurred 20–46 days after the onset of methotrexate and was preceded by luteal activity. A control hysterosalpingography performed 2 months later showed that in the four patients who received medical treatment only, the Fallopian tube was patent, and three became pregnant within 1 year of the methotrexate therapy. One of two patients who failed to respond to medical treatment and required surgical treatment, became pregnant 6 months later. Our results suggest that methotrexate is a viable alternative to surgery for interstitial pregnancies. When the initial level of serum HCG is <1000 mIU/ml, the chances that medical treatment will succeed are increased. This suggests therefore that conservative management of interstitial pregnancies with methotrexate can be considered in selected cases, as is currently the position for the more common tubal pregnancies. [ABSTRACT FROM PUBLISHER]