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Research Question: How might time to healthy singleton delivery affect decision-making during infertility treatment?, Design: This was a Delphi consensus investigating expert opinion that comprised three steps. In Step 1, 12 experts developed statements. In Step 2, 27 experts (including 12 from Step 1) voted (online survey) on their agreement/disagreement with each statement (providing reasons). Consensus was reached if ≥66% of participants agreed/disagreed. Statements not reaching consensus were revised and the process repeated until consensus was achieved. In Step 3 details of the final agreed statements were communicated., Results: Twelve statements were developed, and consensus (agreement) was reached on all after one round of voting., Conclusions: Time to healthy singleton delivery should be taken into consideration when making decisions related to infertility treatment, and it is important that fertility treatment is provided in a timely manner, avoiding over- or under-treatment. In all subfertile women <40 years old, IVF outcomes could be optimized by performing up to six single-embryo transfers and certain procedures might reduce time to healthy singleton delivery. These procedures include preimplantation genetic testing for aneuploidies, frozen replacement cycles immediately after failed fresh cycles and use of gonadotrophin-releasing hormone antagonists. Finally, the number of oocytes retrieved should be maximized to increase cumulative live birth rate., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to identify euploid embryos during IVF. The suggested populations of patients that can benefit from it are infertile women of advanced maternal age, with a history of recurrent miscarriages and/or IVF failures. However, a general consensus has not yet been reached.After the clinical failure of its first version based on cleavage stage biopsy and 9 chromosome-FISH analysis, PGD-A is currently performed by 24 chromosome screening techniques on trophectoderm (TE) biopsies. This approach has been clearly demonstrated to involve a higher clinical efficiency with respect to the standard care, in terms of sustained pregnancy rate per transfer and lower miscarriage rate. However, data about PGD-A efficacy calculated on a per intention-to-treat basis, as well as an analysis of its cost-effectiveness, are still missing.TE biopsy is a safe and extensively validated approach with low biological and technical margin of error. Firstly, the prevalence of mosaic diploid/aneuploid blastocysts is estimated to be between 0 and 16 %, thus largely tolerable. Secondly, all the comprehensive chromosome screening (CCS) technologies adapted to, or designed to conduct PGD-A are highly concordant, and qPCR in particular has been proven to show the lowest false positive error rate (0.5 %) and a clinically recognizable error rate per blastocyst of just 0.21 %.In conclusion, there is a sufficient body of evidence to support the clinical application of CCS-based PGD-A on TE biopsies. The main limiting factor is the need for a high-standard laboratory to conduct blastocyst culture, biopsy and vitrification without impacting embryo viability.

Objective: This study aimed to assess the levels of microbial contamination in semen samples before and after the micro swim-up (MSU) procedure in intra-cytoplasmic sperm injection (ICSI). The new method is an upgrade to the classic wash swim-up procedure., Methods: Semen analysis and microbiological tests were carried out before and after the MSU procedure. A total of twenty semen samples were analyzed., Results: Pathogens were observed in semen samples only before MSU and never after ICSI. Microbiological tests revealed a large prevalence of gram-positive cocci [Staphylococcus spp. (n=16, 80%) and viridans streptococci (n=10, 50%)]. The results of this study indicate that direct MSU in ICSI improved the ICSI workflow., Conclusion: The new workflow is faster and more affordable, and is likely to prevent infection problems that could arise from the normal microbial flora of the semen., Competing Interests: CONFLICT OF INTERESTS No conflict of interests have been declared.

Aim: To evaluate the survival outcomes of consecutive patients with locally advanced cervical cancer (LACC) who underwent comprehensive robotic surgery after neoadjuvant chemotherapy (NACT)., Materials and Methods: Since 2009, patients with LACC (FIGO [International Federation of Gynecology and Obstetrics] stages IB2-IIB) were submitted to robotic surgical staging after 3 cycles of NACT. Clinical objective tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, whereas pathologic responses were defined according to the criteria of the European study SNAP01. Univariable and multivariable analyses were performed to assess potential clinicopathologic prognostic factors affecting progression-free survival and overall survival (OS)., Results: During the study period, 32 patients meeting the inclusion criteria were managed. The median (range) age and body mass index were 47.3 (8.6-75.5) years and 22.7 (17.5-37.1) kg/m(2), respectively. Overall, 28.0 (range, 12-58) lymph nodes were retrieved. According to the final pathologic examination, 6 (18.8%) women had positive pelvic lymph nodes, whereas 16 (50.0%) patients achieved an optimal pathological response. After a median follow-up of 36.3 (range, 5.2-71.1) months, 6 (18.8%) patients had a recurrence and subsequently died of disease.Positive nodal status was the only independent predictor of both progression-free survival (12.5 [2.3-69.1]; P < 0.0001) and OS (12.0 [2.0-60.4]; P < 0.0001) at multivariable analysis., Conclusions: Nodal status represents the strongest predictor of survival in women with LACC. Similarly, NACT including 3 agents (TIP [paclitaxel 175 mg/m(2) + ifosfamide 5 g/m(2) + cisplatin 75 mg/m(2)] and TEP [paclitaxel 175 mg/m(2) + epirubicin 80 mg/m(2) + cisplatin 75 mg/m(2)] regimens) warranted better OS than those achieved by other schedules.

Background: Preimplantation genetic diagnosis (PGD) currently relies on biopsy of one or few embryo cells. Our aim was to evaluate the embryo extracellular matrices (spent medium and blastocoele fluid) as source of DNA for embryo genotyping., Results/methodology: We first evaluated the amplifiability and the amount of genomic DNA in spent embryo culture media from day 3 (n = 32) and day 5/6 (n = 54). Secondly, we evaluated the possibility to genotype the MTHFR polymorphism C677T from media at day 5/6 (n = 8) and blastocoele fluids (n = 9) by direct sequencing. The C677T polymorphism detection rate was 62.5 and 44.4% in medium and fluid, respectively., Conclusion: A noninvasive approach for embryo genotyping was possible, but still with limitations due to low detection rate and possible allele dropout., Competing Interests: Financial & competing interests disclosure This work was supported by funds of the Department of Biomolecular Sciences of University of Urbino. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Purpose: To evaluate whether the in vitro incubation of spermatozoa with myoinositol may improve the fertilization rate in ICSI cycles., Methods: This is a prospective, bicentric, randomized study on 500 MII sibling oocytes injected in 78 ICSI cycles performed between March and October 2013. Randomization of the oocytes into two groups was performed at the time of the denudation. Fertilization rates (per oocyte injected with spermatozoa treated with myoinositol versus per oocyte injected with spermatozoa treated with placebo) were measured as primary outcome and embryo morphology as secondary outcome. Clinical outcomes were also documented., Result (s): Fertilization rate (78.9 ± 28.6% vs 63.2 ± 36.7, P = 0.002) and percentage of grade A embryos on day 3 (59.8 ± 35.6% vs 43.5 ± 41.5, P = 0.019) were significantly higher when spermatozoa were treated in vitro with myoinositol versus placebo. No differences were found for the expanded blastocyst formation rate., Conclusion (s): In vitro treatment of spermatozoa with myoinositol may optimize ICSI outcomes by improving the fertilization rate and embryo quality on day 3. The improvement of the number and the quality of embryos available in an ICSI cycle may have clinical utility if these findings can be confirmed.

Ovarian stimulation is used with IVF/intracytoplasmic sperm injection (ICSI) cycles to obtain multiple oocytes and improve pregnancy rates; however, it also induces perturbation in the oxidant-antioxidant balance leading to oxidation stress. The present study monitored the plasma antioxidant status in women undergoing a long agonist protocol of ovarian stimulation at three different time points: at baseline (T0), after pituitary suppression (T1) and on the day of oocyte retrieval (T2). The antioxidant composition of follicular fluid samples collected on T2 was also evaluated. Significant decreases (P < 0.05) of plasma vitamin C, vitamin E and carotenoids were found between T1 and T2 but not between T0 and T1. At T2, high plasma vitamin E was associated with high numbers of total and mature oocytes retrieved per patient, which, in turn, were favourable for achieving pregnancy. Accordingly, women who became pregnant presented higher vitamin E concentrations both in plasma and FF than those who did not. In conclusion, this study confirmed the occurrence of significant modifications of the plasma antioxidant profile during ovarian stimulation with gonadotrophins; at the same time, it was found that both systemic and follicular antioxidant status may be related to IVF/ICSI outcome., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

IVF often requires embryo cryopreservation through vitrification. During the vitrification process, the embryos can be collapsed by withdrawing the blastocoele fluid. The metabolomic profile of blastocoele fluid has been recently investigated by high-performance liquid chromatography-electrospray ionization-mass spectrometry to provide metabolite information that can help estimations of implantation efficiency. However, the presence of embryo DNA in blastocoele fluid has not been reported to date. This study shows using real-time PCR that genomic DNA was present in about 90% of blastocoele fluid samples harvested during the vitrification procedure. Moreover, the potential for determining embryo sex directly from blastocoele fluid is demonstrated by amplifying the multicopy genes TSPY1 (on the Y chromosome) and TBC1D3 (on chromosome 17). This opens up the possibility of screening embryos from couples carrying an X-linked disorder to identify male embryos at high risk of disease. The application of whole-genome amplification technologies to fluid samples is also shown to be feasible, potentially allowing more comprehensive genetic tests. As proof of principle, microarray comparative genomic hybridization was attempted to confirm the sex of embryos as well as detect several aneuploidies. However, further studies are needed to validate this approach and confirm that the accuracy is sufficient for diagnostic purposes., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aim: The aim of our work was to assess the feasibility and possible benefits of a novel hybrid surgical technique in rectosigmoidal resection in patients with bowel endometriosis., Material and Methods: A total of seven symptomatic and infertile women with severe bowel endometriosis underwent segmental bowel resection using the da Vinci surgical system and conventional laparoscopy. Statistical analysis was performed by Friedman test for non-parametric multiple comparisons., Results: The surgical procedure has a determined short mean operative time (210min) and short postoperative hospitalization (five days). In 100% of patients, the resected area showed disease-free margins. Follow-up, carried out at three, six and 12months after operation, showed a regression of painful symptoms in all operated patients (100%). Two patients (28.6%) aged≥35years eventually had natural pregnancies., Conclusion: To the best of our knowledge, this report is the first concerning the use of a hybrid technique for intestinal resection in severe endometriosis, and comparing our data with that in the literature, its methodological and clinical advantages are evident. Moreover, the complete removal of endometriotic implants seems to offer good results in terms of postoperative fertility, although the study data do not allow us to draw definitive conclusions on the management of fertility., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Oxidative stress plays a fundamental role in the aetiology of male infertility by negatively affecting sperm quality and function. Assessment of blood and seminal plasma oxidative profiles might be a valuable tool to improve evaluation of sperm reproductive capacity and functional competence. This study examined the lipid-soluble antioxidant profile and levels of lipid peroxidation both in blood and seminal plasma samples of infertile and fertile males, in relation to semen parameters. Total antioxidant capacity (TAC) and vitamin E concentrations were significantly (P<0.05) lower in seminal plasma of infertile men compared with fertile subjects; concurrently, a significant accumulation of malondialdehyde was found in infertile patients (P=0.032 compared with controls), which was negatively correlated with sperm motility and morphology. In blood samples, infertile men presented lower concentrations of TAC, carotenoids and vitamin E than fertile subjects; TAC and carotenoids were positively correlated with sperm motility, morphology and concentration. Finally, blood TAC and vitamin E concentrations were positively correlated with the corresponding seminal values, confirming the close relationship between blood and semen antioxidants. All these results indicated the possibility of using not only seminal antioxidants but also blood antioxidants as biochemical markers to support sperm quality evaluation. Oxidative stress induced by reactive oxygen species (ROS) has been widely recognized as one of the major causes of male infertility; indeed, excessive ROS production can negatively impact sperm quality and function. The assessment of blood and seminal plasma oxidative profiles has been suggested as a valuable tool to improve the evaluation of sperm reproductive capacity and functional competence in infertile men. With this in mind, in the present study we examined the lipid soluble antioxidant profile (carotenoids and vitamins A and E) and the levels of lipid peroxidation (malondialdehyde; MDA) both in blood and seminal plasma samples of infertile and fertile males, in correlation with semen parameters namely motility, morphology and concentration. As a result, we obtained evidence that the total antioxidant capacity (TAC) and the concentrations of vitamin E of seminal plasma samples were significantly lower in infertile men than in fertile subjects; at the same time, a significant accumulation of MDA was found in infertile patients. MDA, in turn, negatively correlated with sperm motility and morphology, thus confirming that oxidative damage to lipids impairs sperm quality. In blood samples, infertile men presented lower TAC and lower concentrations of carotenoids and vitamin E than fertile subjects; interestingly, TAC and carotenoid concentrations were positively correlated with sperm motility, morphology, and concentration, confirming the close relationship between blood antioxidants and sperm quality. In conclusion, all these results suggested that the examination of blood and semen oxidative profiles might furnish useful information on sperm quality and function in infertile men., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aims: To evaluate the feasibility and safety of robotic radical parametrectomy (RRP) and pelvic lymphadenectomy for the management of occult invasive cervical cancer or local recurrence of endometrial cancer and to compare our outcomes with the evidence available in the literature., Methods: Starting from 07/2008 consecutive patients submitted to RRP have been included in this study. A comprehensive literature review of published papers about this subject was carried out., Results: During the study period 11 patients were managed; 7 and 4 patients had an occult cervical cancer and a vaginal recurrence of endometrial cancer, respectively. One intra-operative and one post-operative complications were recorded. Neither conversion to laparotomy, nor blood transfusions occurred. Three women required further adjuvant therapies. After a median follow-up of 19 months (range 8-36) one recurrence has been detected. The outcomes of other 200 women from 15 different papers have been collected and compared to our findings., Conclusions: Robotic surgery represents an effective alternative to accomplish radical parametrectomy with comparable results of those reported in the literature in terms of feasibility and safety. RRP is certainly a demanding procedure which however avoids radiotherapy in more than 80% of cases., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Embryo assessment is currently performed through the analysis of morphology and cleavage rate. Recent studies have sought to identify a correlation between quali-quantitative profiles of small molecules of metabolic interest and the outcome of embryo transfer. Approaches relying on both optical and non-optical spectroscopy have been proposed to non-invasively monitor the embryo culture media. However, the non-invasive approach only offers an indirect strategy to monitor embryos and a turn-around solution to bypass the limits of detection of these analytical techniques. In this paper we pave the way for direct metabolic assessment of embryos through the mass-spectrometry-based analysis of blastocoele fluid, which is withdrawn from the blastocoele cavity prior to cryostorage of blastocysts. We conclude that it is possible to detect most of the metabolites of potential interest right at the very heart of the blastocyst, without disrupting the workflow of a classic laboratory pipeline.

Background: In recent years the number of reconstructive procedures for pelvic organ prolapse (POP) through robotic surgery has constantly increased. This paper describes the technical aspects of robotic hysteropromontopexy using the da Vinci surgical system., Methods: Two consecutive 35-year-old patients with POP, who wished to preserve the uterus, underwent hysteropromontopexy by robotic surgery., Results: Both procedures were performed successfully using a robotic approach. No additional reconstructive procedures were thought to be necessary at the end of surgery. Neither intra- nor post-operative complications occurred. After a follow-up of 18 and 6 months for case 1 and 2, respectively, both patients declared themselves satisfied with the anatomical and functional results achieved., Conclusions: This procedure represents an effective option for the management of POP in selected women requiring fertility-sparing options., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: Endometriosis is a frequent indication for in vitro fertilization and embryo transfer (IVF-ET). Its influence on IVF-ET cycles remains controversial. We evaluated the impact of the severity of endometriosis on IVF-ET cycles in young women., Design: Retrospective cohort study., Setting: Academic tertiary referral centre., Sample and Methods: In a retrospective cohort analysis, 164 IVF-ET cycles in 148 women with endometriosis-associated infertility were analyzed. Eighty cycles performed during the same period on 72 consecutive women with tubal infertility were considered as controls. All patients were younger than 35 years old., Main Outcome Measures: Response to controlled ovarian hyperstimulation (COH), number of oocytes retrieved, fertilization, implantation and pregnancy rate (PR)., Results: Clinical PR was lower in the group with endometriosis (all stages) in comparison with the tubal factor group. Higher total gonadotropin requirements, lower response to COH and lower oocyte yield were also found in the endometriosis group. Stage-stratified analysis showed a lower fertilization rate in stage I-II (52.6% stage I-II, 70.5% stage III-IV and 71.9% tubal factor). In stage III-IV endometriosis there was a higher cycle cancellation rate, a reduced response to COH and a lower PR compared with both the stage I-II and the tubal infertility groups (PR 9.7, 25 and 26.1%, respectively)., Conclusions: Stage III-IV was strongly associated with poor IVF outcome. A decreased fertilization rate in stage I-II might be a cause of subfertility in these women, owing to a hostile environment caused by the disease., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure., Methods: In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated., Results: From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002)., Conclusions: Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

The implementation of early detection protocols and advanced treatment strategies has significantly improved survival outcomes for gynecologic cancer patients. The improvement of oncological outcomes has led to an increased attention toward Quality of Life issues, including the childbearing potential for young women. Traditionally the surgical treatment of cervical, endometrial and ovarian cancers involves the removal of the uterus and adnexa, irrespective of the impact on fertility and parenthood and regardless of patient desires. For young women affected by gynecological malignancies at an apparently early stage, fertility-sparing procedures could be offered. The aim of our review is to going through the available evidence in the Literature and to evaluate the current state of art regarding fertility-sparing procedures for women with gynecological malignancies in terms of oncological and fertility outcomes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Oocyte donation is now a useful option for women who cannot start a spontaneous pregnancy for reasons related to advanced age, iatrogenic factors, early depletion of ovarian reserve, or genetic disorders. Embryo implantation rates, pregnancy rates, and pregnancy outcomes among women included in oocyte donation programs were shown to be comparable to those of spontaneous or in vitro fertilization (IVF) pregnancies. With oocyte freezing and cryobanks, recipients may have a successful response to oocyte donation, with no need to be on waiting lists, access to a larger number of oocytes from the same donor, and a lesser risk of infectious disease transmission., (© 2011 New York Academy of Sciences.)

Ovarian hyperstimulation syndrome (OHSS) is a morbid, iatrogenic, and potentially lethal condition caused by the pharmacological induction of ovulation. In OHSS, the ovaries are the site of significant stromal edema with bilateral cystic ovarian enlargement. It has been suggested that ascitic fluid accumulation may be due to increased capillary permeability, which results in fluid shift from the intravascular to the extravascular compartment. While the exact etiology is not clear, several biochemical markers are considered to be possible mediators. There is an incidence of OHSS in about 3% to 8% of all therapy cycles. Severe OHSS is the rarest form, with an incidence characterized by a degree of variability ranging from 0.1% to 2.5% of women subjected to induced polyovulation., (© 2011 New York Academy of Sciences.)

The implantation rate is reduced in the human species and a great number of embryos present developmental anomalies. The past, present, and future of artificial reproductive technology (ART) strategies to improve the chances of implantation are discussed, in addition to the social, clinical, and epidemiological aspects of a progressively lower human fertility potential. The increasing age of couples looking to become pregnant for the first time, and the general tendency of deferring motherhood, are aspects that only a long-term social policy can address. A general proposal for oocyte and sperm cryopreservation is discussed as an option to reduce the impact of age and the possible risks of unethical use of gamete donation. Investing in gamete banking resources may be a unique option for the future., (© 2011 New York Academy of Sciences.)

Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility., (© 2011 New York Academy of Sciences.)

Within the past few years, developmental scientists have switched their attention from the study of DNA sequencing to the epigenetic state of the genome. Studying epigenetics could present the key to understanding gene expression changes without altering the basic structure of DNA. For example, the blastocyst, trophectoderm, and inner cell mass grow within the same environment, having the same genome, but differentiate differently. Each stage of embryo development is characterized by a specific epigenetic pattern. These modifications give the embryos the ability to interact with the uterus. Gene expression profiles change dramatically, and chromatin remodeling allows for core histone elements to undergo significant modifications. In the past, epigenetic mechanisms were studied using less accurate technologies such as PCR techniques and gel electrophoresis. Today microarray, DNA analyzers, and other in silico approaches give us the capability to understand the epigenetic impact on differentiation and cell fate., (© 2011 New York Academy of Sciences.)

The availability of computer-controlled artificial hearts, kidneys, and lungs, as well as the possibility of implanting human embryos in ex vivo uterus models or an artificial endometrium, presents new perspectives for creating an artificial uterus. Survival rates have also improved, with fetuses surviving from as early as 24 weeks of gestation. These advances bring new opportunities for complete or partial ectogenesis through the creation of an artificial womb, one that could sustain the growth and development of fetuses outside of the human body., (© 2011 New York Academy of Sciences.)

Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.

Objective: To evaluate the role of parturition in the recurrence of endometriosis., Design: Retrospectively analyzed, prospectively obtained data., Setting: Unit of Physiopathology of Reproduction, Health Care Unit of Rimini, and University of Bologna Cervesi General Hospital, Cattolica, Italy., Patient(s): Three hundred forty-five patients with stage II-IV endometriosis, dysmenorrhea, and infertility were treated for endometriosis and divided into four groups according to parity and mode of parturition., Intervention(s): The patients were laparoscopically treated for endometriosis upon the occurrence and recurrence of the disease. Ultrasound measurements of the uterine internal ostium (IOS) were performed at each study interval., Main Outcome Measure(s): Degree of dysmenorrhea, occurrence and recurrence of endometriosis, and uterine IOS measurements were established and related to parity and mode of parturition., Result(s): After parturition, dysmenorrhea recurrence was significantly higher in nulliparous women than in women with vaginal parturition. The endometriosis recurrence rate was higher in women who did not have vaginal parturition. The IOS significantly enlarged after vaginal delivery but not after cesarean delivery. There were significant negative correlations between IOS and the recurrence of endometriosis and dysmenorrhea. Odds ratios indicated that as the IOS enlarged, the risk of recurrence decreased., Conclusion(s): Vaginal parturition plays a protective role in the recurrence of endometriosis., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Conscious sedation, used with or without peripheral or central blocks, is an elective anesthetic technique used for many outpatient procedures. The aim of this study was to evaluate the effects of a single pre-anesthetic dose of betamethasone (4 mg) on intraoperative and postoperative pain in 380 women, 18 to 75 years old, undergoing gynecologic and obstetric surgery (diagnostic curettage, operative and diagnostic hysteroscopy, conization, minilaparoscopy, cone biopsy, endometrial ablation, assisted reproduction techniques, and induced and therapeutic abortion) in a outpatient service. In this randomized, double-blind, placebo-controlled study, the patients were divided into two equal groups according to a computer-generated randomized list. One group received 4 mg of betamethasone i.v. as a premedication (group B), whereas the placebo group (group P) received only saline. All patients underwent the same sedation, associated with a peripheral block. Pain was evaluated using a 5-point verbal rating scale during surgery, after 2 h, and on discharge. In group B, intraoperative and postoperative pain was significantly less frequent than in group P (P < 0.001). Consequently, fewer women belonging to group B requested additional analgesic drugs during and after surgery (P < 0.01). Patients in group B also experienced a greater degree of satisfaction (P < 0.01). Briefly, a single dose of betamethasone seemed to reduce the incidence and severity of perioperative pain after gynecologic outpatient surgery.

The assessment of the standard for success of in vitro fertilization (IVF) treatment is an arduous task. Clinical efficiency and safety of a given procedure should represent fundamental tools for objective comparison. However, differences in patient populations, laboratory protocols, and expression of clinical data make the analysis of different studies and strategies very difficult. Formulation of the standard for success through the cumulative delivery rate per cycle of stimulation is a very attractive option because it includes the essential contribution of frozen embryos, which can represent 30-40% of all deliveries, while taking into account the need to minimize the proportion of pharmacological and surgical treatments. Embryo cryopreservation may be applied at different postinsemination stages. Larger and more detailed sets of data are available for day 2 embryo freezing, which allows cumulative delivery rates of 50-60% in good prognosis patients. In the last few years, novel freezing methods have improved the overall efficiency of oocyte cryopreservation. Especially in contexts afflicted by legal restrictions to embryo cryo- preservation, this form of preservation has started to have an impact on the IVF standard of success, generating cumulative pregnancy rates approaching 50%. Despite having been applied systematically by some IVF programs for only a few years, oocyte freezing already competes in efficiency with pronuclear-stage cryopreservation, and it does not appear unrealistic to predict that in the future it will challenge the dominance of embryo cryopreservation as the preferred form of conservation.

Infertile women are examined to exclude tubal occlusion or a pelvic factor through indirect tests, such as hysterosalpingography (HSG), sonohysterosalpingography/hysterosalpingosonography (SH), and/or laparoscopy (Lps). Assisted reproductive technologies (ART) are proposed to resolve infertility according to the results of the above-mentioned diagnostic procedures. Today, Lps still represents the second option after several failures of in vivo attempts and before moving to conceive in vitro. The aim of this study was to establish the diagnostic power of HSG and SH compared with that of Lps and the efficacy of ART when each single test is used as an inclusion criterion. We recruited 2560 infertile women (aged 20 to 35) to undergo diagnostic and therapeutic procedures to address their infertility in our clinical theatre. Of these, 1080 women underwent Lps and hysteroscopy (Group 1), 525 underwent HSG (Group 2), and 955 underwent SH (Group 3). The positive and negative predictive values of sonosalpingosonography were 75.8% and 91.2% and those of hysterosalpingography were 71.8% and 88.2%, respectively. Endometriosis (stage II-IV of the revised American Society for Reproductive Medicine [ASRM] classification) was diagnosed laparoscopically in 344 out of 1080 women (32%). Only 44 women (13%) with endometriosis showed bilateral tubal occlusion. Pelvic factors other than tubal occlusions are neither diagnosed nor treated in a timely manner by indirect tubal patency tests. The conventional use of HSG and/or SH may increase the time required to find an adequate treatment by which to achieve a successful pregnancy.

Purpose of Review: The aim of this article is to assess the importance of uterine contractility in the implantation of human embryos., Recent Findings: Recent findings show that the receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity patterns of the uterus were identified with adequate wave patterns appearing to be related to successful reproduction in spontaneous cycles and in assisted reproduction. Such patterns are controlled by steroid hormones. Embryo attachment to the predecidualized endometrium and its invasion may be determined by the expression of proteolytic enzymes that require uterine quiescence for implantation. The uterine activity was detected both in vitro and in vivo by using invasive intrauterine pressure and noninvasive ultrasound approaches. Progesterone promotes local vasodilatation and uterine musculature quiescence by inducing nitric oxide synthesis in the decidua. At present, until new evidence emerges to demonstrate otherwise, the effects of progesterone are, directly or indirectly, the only determinant of endometrial preparation for embryo nidation, with the induction of uterine quiescence being one of these effects., Summary: Adequate uterine contractility may provide for gamete/embryo transportation through the utero-tubal cavities and successful embryo implantation in spontaneous or assisted reproduction. Inadequate uterine contractility may lead to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and endometriosis.

Objective: The objective was to verify the outcome of intracytoplasmic sperm injection (ICSI) with ovulation induction performed with GnRH antagonists, comparing the use of recombinant follicle-stimulating hormone (r-FSH) alone and in combination with recombinant luteinizing hormone (r-LH) in a prospective and randomized trial., Study Design: Forty male-factor infertile normo-ovulatory patients undergoing ovarian stimulation for ICSI took part in the study. After initiating ovarian stimulation with only r-FSH, all patients were treated with GnRH antagonist (cetrorelix). When beginning cetrorelix administration, the patients were randomized into two groups: in group I, 20 patients continued to receive r-FSH alone and in group II, 20 patients received combined r-FSH and r-LH. The number of metaphase II oocytes, estradiol concentration at the time of hCG administration, fertilization rate, grade 1 embryo rate, pregnancy rate per cycle, and implantation rate were measured. Results are expressed as mean+/-S.D., Results: In group I, the women's age was 32.3+/-2.30 years, and FSH concentration was 7.8+/-1.7 IU/ml. In group II, the women's age was 32.2+/-2.46 years and FSH concentration was 7.5+/-1.7 IU/ml. The number of oocytes retrieved was 9.6+/-2.9 and the number of metaphase II oocytes was 6.7+/-2.2 in group I. In group II the number of retrieved oocytes were 9.9+/-2.6 and the number of metaphase II oocytes 6.9+/-2.1 (p>0.05). Estradiol concentration at the time of hCG was 4.6+/-1.8 nm/l in group I and 6.7+/-2.0 nm/l in group II (p<0.01). Fertilization rate was 73.0% in group I versus 78.2% in group II. In group I, we obtained 53.9% of grade 1 embryos versus 54.4% in group II (p>0.05). Pregnancy and implantation rates in group I were 30.0 and 16.7%, respectively and in group II 35.0 and 20.4%, respectively (p>0.05)., Conclusions: The use of recombinant LH in addition to recombinant FSH may prevent a decrease in estradiol after GnRH antagonist administration, but does not influence positively the outcome of oocyte number, maturation, embryo quality, fertilization rate, pregnancy rate per cycle, and implantation rate.

Study Objective: Chronic endometritis is a subtle condition that is difficult to detect; however, it may cause abnormal uterine bleeding and infertility. Few data exist about the appearance of chronic endometritis at fluid hysteroscopy and about the value of diagnostic fluid hysteroscopy in the detection of this condition. In our experience, at fluid hysteroscopy chronic endometritis is characterized by consistent association of stromal edema and either focal or diffuse hyperemia; in some cases, this finding is associated with endometrial micropolyps (less than 1 mm in size). This study attempted to describe diagnostic criteria for chronic endometritis at fluid hysteroscopy and assess the diagnostic accuracy of fluid hysteroscopy in the detection of this condition., Design: Retrospective Study (Canadian Task Force classification II-2)., Setting: University hospital., Patients: Nine hundred-ten women in whom hysteroscopy was indicated., Interventions: Fluid hysteroscopy followed by endometrial biopsy., Measurements and Main Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of fluid hysteroscopy in the detection of chronic endometritis, based on the association of edema; hyperemia; and, if present, micropolyps were calculated. Based on the presence of hyperemia and edema, chronic endometritis was diagnosed in 158 patients (17.4%); in 61 patients (6.7%), micropolyps also were present. Histology confirmed the diagnosis in 101 patients (63.9% of positive cases at hysteroscopy) and was positive in 9 additional cases not detected by hysteroscopy. Chronic endometritis at histology was found in approximately 30% of infertile women and 35% of cases related to abnormal uterine bleeding. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for chronic endometritis based on detection of only hyperemia and edema were 91.8%, 92.9%, 63.9%, and 98.8%, respectively; the diagnostic accuracy was 92.7 %. The combination of hyperemia, edema, and micropolyps had sensitivity, specificity, and positive and negative predictive values of 55.4%, 99.9%, 98.4%, 94.5%, respectively, with a diagnostic accuracy of 93.4%., Conclusions: Fluid hysteroscopy is very reliable in diagnosing no inflammation, while detection of micropolyps is a very reliable sign of inflammation. When performing hysteroscopy for abnormal uterine bleeding or infertility, signs of chronic endometritis should always be sought.

The receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the interleukin-1 system (IL-1). Embryo attachment is the result of adhesion protein expression, and the invasion of the embryo is governed by proteolytic enzymes. Leukaemia inhibitory factor (LIF) is produced by natural killer lymphocytes that interact with the invading trophoblast. This may activate urokinase plasminogen activator (uPA) and gelatinase enzymes, which play a crucial role in trophoblast invasion. Oestrogen stimulates, while progesterone inhibits, LIF. The role of endometrial contractility in displacing human embryos from the Fallopian tube to the lumen cavity of the uterus or vagina in terms of pregnancy or wastage is still a matter of discussion. Endometriosis and its associated abnormal uterine contractions may be also linked to implantation failure. Unless new evidence emerges to indicate otherwise, it can be assumed that progesterone is, either in a direct (non-genomic: contractility) or indirect (genomic: decidualization) manner, the only determinant of endometrial priming necessary for embryo nidation.

Purpose of Review: The aim of this article is to assess the importance of uterine contractility in the implantation of human embryos., Recent Findings: Recent findings show that the receptive phase of the endometrium seems to occur in close association with the appearance of pinopodes and endometrial integrins that may be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity patterns of the uterus were identified with adequate wave patterns appearing to be related to successful reproduction in spontaneous cycles and in assisted reproduction. Such patterns are controlled by steroid hormones. Embryo attachment to the predecidualized endometrium and its invasion may be determined by the expression of proteolytic enzymes that require uterine quiescence for implantation. The uterine activity was detected both in vitro and in vivo by using invasive intrauterine pressure and noninvasive ultrasound approaches. Progesterone promotes local vasodilatation and uterine musculature quiescence by inducing nitric oxide synthesis in the decidua. At present, until new evidence emerges to demonstrate otherwise, the effects of progesterone are, directly or indirectly, the only determinant of endometrial preparation for embryo nidation, with the induction of uterine quiescence being one of these effects., Summary: Adequate uterine contractility may provide for gamete/embryo transportation through the utero-tubal cavities and successful embryo implantation in spontaneous or assisted reproduction. Inadequate uterine contractility may lead to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and endometriosis.

Uterine fibroids have been reported in 27% of infertile women, and 50% of women with unexplained infertility become pregnant after myomectomy. The age at which a first pregnancy occurs is increasing from the thirties to the forties. This increase and the recurrence rate of leiomyomas from 15 to 30% points to the effect of myomas on the infertility. Mechanisms by which myomas may cause infertility are abnormal uterine contractility, elongation of the uterine cavity, and distortion of uterine vascularization. Surgery may have beneficial or adverse effects without clear data on its effect on the assisted reproductive technology (ART) procedures. The present study was undertaken to establish the impact of surgical removal of myomas on fertility and infertility of patients undergoing ART procedures. Patients who underwent surgical removal of myomas before in vitro fertilization (Group A) had a cumulative success rate of 33% for one to three procedures (28 clinical pregnancies in 84 patients) and delivery rate of 25% (21 live births in 84 patients). Patients who underwent in vitro fertilization without previous surgery (Group B) had a 15% clinical pregnancy rate (13 pregnancies in 84 patients) (P < 0.05) and 12% delivery rate (10 deliveries in 84 pregnancies) (P < 0.05). Abortion rates were 7% (8 deliveries in 84 patients) and 4% (3 deliveries in 84 patients) in Groups A and B, respectively. This study confirms the beneficial effect of surgical removal of fibroids before undergoing ART procedures.

Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P < 0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P < 0.05). In conclusion, patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.

The nonpregnant uterus shows uterine activity throughout the menstrual cycle. This uterine activity was detected both by single strep tissue and by using intrauterine pressure recordings in vitro and in vivo. Today, ultrasound has made it possible to study this activity with a noninvasive approach and to assess uterine contractions (UCs) in real-time movements of the uterus. Throughout the menstrual cycle, wavelike activity patterns of the reproductive organ were established. These patterns are under control of steroid hormones. Adequate UCs may provide for gamete/embryo transportation throughout the uterotubal cavities and successful embryo implantation in spontaneous and/or assisted reproduction. Inadequate UCs may produce ectopic pregnancy, miscarriages, retrograde bleeding with dysmenorrhea, and endometriosis.

Pain control during labor is a primary objective of antalgic therapy. The use of the peridural as an elective procedure for labor analgesia is now corroborated by the international scientific community. Sometimes a combined spinal-peridural procedure is used together with the intrathecal administration of opioids to also cover the first stage of labor. Unfortunately, patients and/or gynecologists often request analgesia in a late stage of labor. The aim of our study was to evaluate the possibility of using a subarachnoid block alone for labor analgesia when this is requested at a late stage, that is, in advanced labor with cervical dilation greater than 7 cm. After approval by our ethics committee and the written and informed consent of the patients, 111 women were enrolled in this study and randomly divided into two groups. The first group (Group S: 55 patients) received a subarachnoid block with 2.5 mg hyperbaric bupivacaine + 25 mug fentanyl + 1 mL 10% glucose. A pudendal nerve block with 7 mL 2% mepivacaine in each side was administered to the second group (Group P: 56 patients). In both groups, careful maternal-fetal monitoring was conducted, and pain was scored on a numerical scale from 0 to 4, 10 minutes after placement of the block (time [T] 0), at delivery (T1), and at episiorrhaphy (T2). In all patients, we recorded any side effects, the Apgar score at birth and after 5 minutes, the administration of other analgesic and/or sedative drugs, the degree of satisfaction, and the time of hospitalization after delivery. Evaluations were performed by anesthesiologists unaware of patients' treatment group. The duration of spinal analgesia was considered to be the time from injection of study drugs to the time of the patient's first request for additional analgesia. In no cases were there any side effects worthy of note, and hospitalization never exceeded 72 hours. The Apgar score was always between 7 and 10. All except one of the women in Group S were satisfied or more than satisfied with their pain management, whereas 50 women in Group P expressed only moderate satisfaction or dissatisfaction (P < 0.0001). In most patients in Group S, complete analgesia was obtained. In Group P, however, 10 minutes after placement of the pudendal nerve block, 40 patients reported no improvement in pain symptomatology during contractions and only 16 reported less painful contractions (P < 0.0001). The duration of spinal analgesia (128 +/- 38 minutes) was enough in most cases for delivery to be completed. These results suggest that low-dose bupivacaine-fentanyl spinal analgesia represents an important option for pain relief in late labor, not the least because the procedure does not upset the dynamics of delivery or alter vital parameters and is welcomed by women in labor who are still able to collaborate actively in the birth of their baby.

In this article, we review the literature and our personal experience regarding the many factors that appear to influence implantation rate. Oocyte quality, as determined by patient age and aneuploidies, probably plays a major role in RIF. However, a panoply of other factors have been brought under investigation, quite often with contradictory results and additional intriguing questions to be studied. Infections of the vagina, cervix, and endometrium, the role of mucus aspiration and washing of the cervix on transfer, the role of catheter guidance for a correct transfer and potion of embryos, the effect of mock transfer, and the role of hysteroscopy and its timing before transfer procedures are analyzed both as a review of the literature and as opinions and data from our experience. Many of these factors are interlaced and from the apparently simple issue of trauma, to infections and immune modulation of hatching and implantation, a biological continuum can easily be identified. The impact of abnormalities of the immune system and of homeostasis abnormalities is also covered in a brief overview of reported works and our experience. These latter areas probably constitute the common biological background of all other external factors that, however, the skilled must equip themselves for improving implantation success.

Embryo transfer has received little clinical attention and has been, until recently, the most inefficient step in in-vitro fertilization (IVF). In this article, the authors review the literature and their personal experience regarding the process of intrauterine transfer of embryos, which remains the object of much discussion. Factors which appear to influence implantation rates are: contamination of the catheter tip with cervical bacteria, stimulation of uterine contractions during the procedure, the type of catheter, ultrasound guidance during the transfer, and the position of the embryos in the uterine cavity. Easy and atraumatic transfer is essential for successful implantation and the embryos need to be placed in the middle of the cavity, away from the fundus. Knowing, beforehand, the position and length of the uterus can provide better results and may reduce the rate of ectopic pregnancies. Evidence from randomized studies has supported this claim. Despite the number of available studies controlling certain variables, most authors, even using the same catheter, ultrasound guidance and/or a trial transfer use different protocols or similar instruments in different ways. Standardization of the transcervical intrauterine transfer of embryos in a large randomized study is needed before definitive conclusions can be drawn. The goal of improved implantation and pregnancy rates deserve these efforts.

Objective: To establish the role of uterine contractions in retrograde menstruation with subsequent abdominal implantation of endometrial tissue., Design: Controlled prospective study., Setting: University hospital-based study., Patient(s): Infertile women with (n = 22) and without (n = 22) endometriosis., Main Outcome Measure(s): Frequency, amplitude, and basal pressure tone of uterine contractions; correlation of contractions with retrograde bleeding and presence of viable endometrial cells; and dysmenorrhea before and 3 and 24 months after surgery., Result(s): Compared with controls, patients with endometriosis had uterine contractions with higher frequency (22.73 +/- 5.66 osc/10 min vs. 11.09 +/- 3.26 osc/10 min), amplitude (20.83 +/- 3.94 mm Hg vs. 6.77 +/- 2.83 mm Hg), and basal pressure tone (50.14 +/- 16.30 mm Hg vs. 24.68 +/- 6.14 mm Hg). Dysmenorrhea was scored as 4.09 +/- 1.44 in patients with endometriosis and 0.86 +/- 1.42 in controls. Retrograde bleeding was found in 73% of patients with endometriosis vs. 9% of controls, and only 45% of patients with endometriosis had viable endometrial cells in the cul-de-sac., Conclusion(s): Endometriosis may result from abnormal myometrial contractility through tubal transportation, dissemination, and implantation of endometrial viable cells into the abdomen.

Background: The present study was undertaken to evaluate differences between patients with and without eutopic endometrium in the recurrence of ectopic endometriotic implants., Methods: Endometrial ablation (EA) was carried out in 14 women out of 28 laparoscopically treated for endometriosis and recurrence of the disease was evaluated 24 months later. Data were compared using paired Student's t-test and chi2 test., Results: Patients undergoing EA procedures did not exhibit recurrence of endometriosis while nine patients without that procedure had recurrence of the disease (P < 0.001). The endometrial cells found in the debris of the cul de sac of eight patients who did not undergo EA were both stromal and epithelial cells. No blood or blood cells were found in the cul de sac of patients undergoing EA., Conclusions: The present study supports a role of eutopic endometrium in the recurrence of endometriosis through tubal dissemination of endometrial debris and implantation of endometrial cells into the abdomen.

Recent renewed interest in uterine contractility stems from the possibility of directly visualizing uterine contractility on images generated by high-resolution ultrasound probes. During the menstrual cycle, three typical patterns of uterine contractility have been recognized. During the luteofollicular transition and early follicular phase (menses), the contractile event involves all layers of the myometrium and exerts antegrade (from fundus to cervix) expulsive forces. Characteristically, uterine contractions are often perceived by women at the time of menses, sometimes reaching the level of painful cramps (dysmenorrhea). In the late follicular phase, uterine contractility involves only the subendometrial layers of the myometrium and is never perceived by women. The primary function of uterine contractility in the late follicular phase is to facilitate the retrograde (cervix to fundus) transport of sperm towards the distal end of the fallopian tubes where fertilization normally takes place. Finally, the uterus reaches a stage of quiescence after ovulation (under the influence of progesterone) that characterizes the major part of the luteal phase. The present review summarizes our understanding of the physiological role of uterine contractility during the follicular phase and the possible implications in pathological circumstances such as endometriosis and dysmenorrhea.

Spontaneous uterine contractility during the menstrual cycle is required for menstruation, gamete transport, and, most likely, embryo nidation. Abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. Based on previous studies with progesterone, we have postulated the existence of a portal system that is responsible for some degree of direct vagina-to-uterus transport of administered compounds (i.e., the "first uterine pass effect"). It is possible that treatment with uterorelaxing substances, particularly beta-adrenergic agonists, may alleviate the uterine discomfort that accompanies dysmenorrhea. However, side effects encountered with oral administration of beta-agonists limit their utility. Alternatively, vaginal delivery of beta-agonists could solve this dilemma by enhancing their efficacy and reducing side effects. Therefore, in the current study we used hysterectomy specimens and an in vitro uterine perfusion system to test the vagina-to-uterus transport of [3H]terbutaline, a well-known beta-agonist. With the use of autoradiographic and scintillation counting techniques, our results clearly show progressive diffusion of labeled terbutaline from the rim of vaginal tissue through the uterus during the first 12 hours of perfusion. This indicates that uterine targeting of terbutaline can be accomplished through vaginal administration, suggesting a new therapeutic modality in women's health care.

The purpose of this study was to compare, in infertile patients, the efficacy of laparoscopic myomectomy versus abdominal myomectomy, in restoring fertility and to evaluate the obstetric outcomes. Between January 1993 and January 1998, 131 patients of reproductive age, with anamnesis of infertility, underwent myomectomy because of the presence of at least one large myoma (diameter greater than or = 5 cm). Patients were randomly selected for treatment by laparotomy (n = 65) or laparoscopy (n = 66). The two groups were homogeneous for number, size and position of large myomata. Significant differences were found in the post-operative outcome: febrile morbidity (> 38 degrees C) was more frequent in the abdominal than in the laparoscopic group (26.2 versus 12.1%; P < 0.05). Laparotomy caused a more pronounced haemoglobin drop (2.17 +/- 1.57 versus 1.33 +/- 1.23; P < 0.001); three patients received a blood transfusion after laparotomy and none after laparoscopy. The post-operative hospital stay was shorter in the laparoscopic group (142.80 +/- 34.60 versus 75.61 +/- 37.09 h; P < 0.001). No significant differences were found between the two groups as concerns pregnancy rate (55.9% after laparotomy, 53.6% after laparoscopy), abortion rate (12.1 versus 20%), preterm delivery (7.4 versus 5%) and the use of Caesarean section (77.8 versus 65%). No case of uterine rupture during pregnancy or labour was observed.

The non-pregnant uterus shows different patterns of contractility during the menstrual cycle. A renewed interest in uterine contractility has resulted from reports of non-invasive ultrasound (US) based studies. To clarify the changes in uterine contractility occurring throughout the menstrual cycle, we prospectively studied uterine contractions (UC) at six representative stages with US and intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results showed UC frequency could be measured by either US or IUP. UC amplitude and resting pressure tone could only be assessed by IUP. Conversely, direction of UC displacement could only be assessed by US. UC frequency increased at mid-cycle and decreased throughout the luteal phase suggesting oestradiol and progesterone exert positive and negative actions on uterine contractility, respectively. UC amplitude increased throughout the menstrual cycle to maximum values in the late luteal phase. Retrograde UC were most frequent at mid-cycle and convergent ('opposing') UC predominated during the luteal phase. While the former pattern ensures sperm transport, the latter may facilitate embryo implantation. In conclusion, UC changes throughout the menstrual cycle assessed by US and IUP emphasize the hormonal dependence of uterine contractility. Although UC patterns favouring sperm transport appear regulated by oestradiol, uterine quiescence and the dominance of convergent UC prevailing at the time of implantation are linked to progesterone. These data will serve to identify and treat possible dyskinetic changes in uterine contractility, particularly in women suffering from infertility, endometriosis, and dysmenorrhea.

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.

Objective: To compare progesterone concentrations in serum and endometrial tissue from hysterectomy specimens after vaginal or intramuscular (IM) administration of progesterone gel., Methods: This was a randomized open study of 14 post-menopausal women undergoing transabdominal hysterectomies. Participants received either vaginal progesterone gel, 90 mg, or IM progesterone, 50 mg, at 8:00 AM and 8:00 PM on the day before surgery and at 6:00 AM on the day of surgery. Venous blood samples for progesterone measurement were collected at 8:00 AM on the day before surgery (baseline) and during surgery. After removal of the uterus, the endometrium was sampled from the anterior and posterior walls. Results were expressed as ratios of endometrial to serum progesterone concentrations x 100., Results: Ratios of endometrial to serum progesterone concentrations were markedly higher in women who received vaginal progesterone (14.1 median, 8.5-59.4 range; 95% confidence interval [CI] 9.89, 38.79) compared with IM injections (1.2 median, 0.5-13.1 range; 95% CI -0.48, 7.39) (P < .005)., Conclusion: Ratios of endometrial to serum progesterone concentrations were higher after vaginal administration of progesterone than after IM injections. Our findings in endometrial tissue specimens from hysterectomies excluded the possibility of contamination by progesterone that remained in the vagina.