The artificial uterus: on the way to ectogenesis.

The inability to support the growth and development of a mature fetus up to delivery results in significant human suffering. Current available solutions include adoption, surrogacy, and uterus transplantation. However, these options are subject to several ethical, religious, economic, social, and medical concerns. Ectogenesis is the process in which an embryo develops in an artificial uterus from implantation through to the delivery of a live infant. This current narrative review summarizes the state of recent research focused on human ectogenesis. First, a literature search was performed to identify published reports of previous experiments and devices used for embryo implantation in an extracorporeally perfused human uterus. Furthermore, studies fitting that aim were selected and critically evaluated. Results were synthesized, interpreted, and used to design a prospective strategy for future research. Therefore, this study suggests that full ectogenesis might be obtained using a computer-controlled system with extracorporeal blood perfusion provided by a digitally controlled heart-lung-kidney system. From a clinical perspective, patients who will derive significant benefits from this technology are mainly those women diagnosed with anatomical abnormalities of the uterus and those who have undergone previous hysterectomies, numerous abortions, and experienced premature birth. Ectogenesis is the complete development of an embryo in an artificial uterus. It represents the solutions for millions of women suffering from premature deliveries, and the inability to supply growth and development of embryos/fetuses in the womb. In the future, ectogenesis might replace uterine transplantation and surrogacy.

Risk of genetic and epigenetic alteration in children conceived following ART: Is it time to return to nature whenever possible?

Assisted reproductive technology may influence epigenetic signature as the procedures coincide with the extensive epigenetic modification occurring from fertilization to embryo implantation. However, it is still unclear to what extent ART alters the embryo epigenome. In vivo fertilization occurs in the fallopian tube, where a specific and natural environment enables the embryo's healthy development. During this dynamic period, major waves of epigenetic reprogramming, crucial for the normal fate of the embryo, take place. Over the past decade, concerns relating to the raised incidence of epigenetic anomalies and imprinting following ART have been raised by several authors. Epigenetic reprogramming is particularly susceptible to environmental conditions during the periconceptional period; therefore, unphysiological conditions, including ovarian stimulation, in vitro fertilization, embryo culture, cryopreservation of gametes and embryos, parental lifestyle, and underlying infertility, have the potential to contribute to epigenetic dysregulation independently or collectively. This review critically appraises the evidence relating to the association between ART and genetic and epigenetic modifications that may be transmitted to the offspring.

Effects of hydrosalpinx on endometrial implantation failures: evaluating salpingectomy in women undergoing in vitro fertilization / Efeitos do hydrosalpinx no falho de implantação endometrial: Avaliar a salpingectomia nas mulheres em curso de fertilização in vitro

Abstract Hydrosalpinx is a disease characterized by the obstruction of the salpinx, with progressive accumulation in the shape of a fluid-filled sac at the distal part of the tuba uterina, and closed to the ovary. Women with hydrosalpinges have lower implantation and pregnancy rates due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Evidence suggests that the presence of hydrosalpinx reduces the rate of pregnancy with assisted reproductive technology. The main aim of the present is review to make an overview of the possible effects of hydrosalpinx on in vitro fertilization (IVF).We conducted a literature search on the PubMed, Ovid MEDLINE, and Google Scholar data bases regarding hydrosalpinx and IVF outcomes. Hydrosalpinx probably has a direct toxic effect on sperm motility and on the embryos. In addition, the increasing liquid inside the salpinges could alter the mechanisms of endometrial receptivity. The window of endometrial receptivity is essential in the implantation of blastocysts, and it triggers multiple reactions arising from the endometrium as well as the blastocysts. Hydrosalpinx could influence the expression of homeobox A10 (HOXA10) gene, which plays an essential role in directing embryonic development and implantation. Salpingectomy restores the endometrial expression of HOXA10; therefore, it may be one mechanism by which tubal

Effects of Hydrosalpinx on Endometrial Implantation Failures: Evaluating Salpingectomy in Women Undergoing in vitro fertilization.

Hydrosalpinx is a disease characterized by the obstruction of the salpinx, with progressive accumulation in the shape of a fluid-filled sac at the distal part of the tuba uterina, and closed to the ovary. Women with hydrosalpinges have lower implantation and pregnancy rates due to a combination of mechanical and chemical factors thought to disrupt the endometrial environment. Evidence suggests that the presence of hydrosalpinx reduces the rate of pregnancy with assisted reproductive technology. The main aim of the present is review to make an overview of the possible effects of hydrosalpinx on in vitro fertilization (IVF). We conducted a literature search on the PubMed, Ovid MEDLINE, and Google Scholar data bases regarding hydrosalpinx and IVF outcomes. Hydrosalpinx probably has a direct toxic effect on sperm motility and on the embryos. In addition, the increasing liquid inside the salpinges could alter the mechanisms of endometrial receptivity. The window of endometrial receptivity is essential in the implantation of blastocysts, and it triggers multiple reactions arising from the endometrium as well as the blastocysts. Hydrosalpinx could influence the expression of homeobox A10 (HOXA10) gene, which plays an essential role in directing embryonic development and implantation. Salpingectomy restores the endometrial expression of HOXA10; therefore, it may be one mechanism by which tubal removal could result in improved implantation rates in IVF. In addition, salpingectomy does not affect the ovarian response, nor reduces the antral follicle count. Further studies are needed to establish the therapeutic value of fluid aspiration under ultrasonographic guidance, during or after oocyte retrieval, in terms of pregnancy rate and ongoing pregnancy.

COVID-19 and ART: the view of the Italian Society of Fertility and Sterility and Reproductive Medicine.

The COVID-19 pandemic is an unprecedented global situation. As assisted reproductive technology (ART) specialists, we should be cautious, carefully monitoring the situation while contributing by sharing novel evidence to counsel our patients, both pregnant women and would-be mothers. Time to egg collection and drop-out rates are critical parameters for scheduling treatments once the curve of infections has peaked and plateaued in each country. In order to reduce the values for these two parameters, infertile patients now require even more support from their IVF team: urgent oocyte collection for oncology patients must be guaranteed, and oocyte retrievals for women of advanced maternal age and/or reduced ovarian reserve cannot be postponed indefinitely. This document represents the position of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) in outlining ART priorities during and after this emergency.

Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment.

Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. At present, no remedies are available to counteract the aging-related fertility decay, however different therapeutic approaches can be offered to women older than 35 year undergoing IVF. This review summarizes the main current strategies proposed for the treatment of AMA: (i) oocyte cryopreservation to conduct fertility preservation for medical reasons or "social freezing" for non-medical reasons, (ii) personalized controlled ovarian stimulation to maximize the exploitation of the ovarian reserve in each patient, (iii) enhancement of embryo selection via blastocyst-stage preimplantation genetic testing for aneuploidies and frozen single embryo transfer, or (iv) oocyte donation in case of minimal/null residual chance of pregnancy. Future strategies and tools are in the pipeline that might minimize the risks of AMA through non-invasive approaches for embryo selection (e.g., molecular analyses of leftover products of IVF, such as spent culture media). These are yet challenging but potentially ground-breaking perspectives promising a lower clinical workload with a higher cost-effectiveness. We also reviewed emerging experimental therapeutic approaches to attempt at restoring maternal reproductive potential, e.g., spindle-chromosomal complex, pronuclear or mitochondrial transfer, and chromosome therapy. In vitro generation of gametes is also an intriguing challenge for the future. Lastly, since infertility is a social issue, social campaigns, and education among future generations are desirable to promote the awareness of the impact of age and lifestyle habits upon fertility. This should be a duty of the clinical operators in this field.

Nociceptor plasticity: A closer look.

Nociceptors are receptors specifically involved in detecting a tissue damage and transducing it in an electrical signal. Nociceptor activation provoked by any kind of acute lesion is related to the release of several mediators of inflammation, within the framework of a process defined as "peripheral sensitization." This results in an exaggerated response to the painful stimulus, clinically defined as "primary hyperalgesia." The concept of "neuroplasticity" may explain the adaptive mechanisms carried out by the Nervous System in relation to a "harmful" damage; also, neuroplasticity mechanisms are also fundamental for rehabilitative intervention protocols. Here we review several studies that addressed the role of different receptors and ionic channels discovered on nociceptor surface and their role in pain perception. The changes in expression, distribution, and functioning of receptors and ionic channels are thought to be a part of the neuroplasticity property, through which the Nervous System constantly adapts to external stimuli. Moreover, some of the reviewed mediators are also been associated to "central sensitization," a process that results in pain chronicization when the painful stimulation is particularly prolonged or intense, and lastly leads to the memorization of the uncomfortable painful perception.

Pre-implantation genetic testing in ART: who will benefit and what is the evidence?

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.

Electronic witness system in IVF-patients perspective.

OBJECTIVE: The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction. DESIGN: The design of this study is a prospective single-center cohort study. SETTING: The setting of this study was located in the private IVF center. PATIENT(S): Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS. INTERVENTION(S): Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6. MAIN OUTCOMES MEASURE(S): Patient concerns about sample mix-up without and with an EWS were assessed. RESULT(S): 90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners (p = 0.029). A significant mix-up event occurred in an Italian hospital during the study and patient's satisfaction increased significantly towards the use of the EWS after the event (p = 0.032). CONCLUSION(S): EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient's perspective.

The Impact of Biopsy on Human Embryo Developmental Potential during Preimplantation Genetic Diagnosis.

Preimplantation Genetic Diagnosis and Screening (PGD/PGS) for monogenic diseases and/or numerical/structural chromosomal abnormalities is a tool for embryo testing aimed at identifying nonaffected and/or euploid embryos in a cohort produced during an IVF cycle. A critical aspect of this technology is the potential detrimental effect that the biopsy itself can have upon the embryo. Different embryo biopsy strategies have been proposed. Cleavage stage blastomere biopsy still represents the most commonly used method in Europe nowadays, although this approach has been shown to have a negative impact on embryo viability and implantation potential. Polar body biopsy has been proposed as an alternative to embryo biopsy especially for aneuploidy testing. However, to date no sufficiently powered study has clarified the impact of this procedure on embryo reproductive competence. Blastocyst stage biopsy represents nowadays the safest approach not to impact embryo implantation potential. For this reason, as well as for the evidences of a higher consistency of the molecular analysis when performed on trophectoderm cells, blastocyst biopsy implementation is gradually increasing worldwide. The aim of this review is to present the evidences published to date on the impact of the biopsy at different stages of preimplantation development upon human embryos reproductive potential.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN: Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS: Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION: Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

The effect of the hormonal milieu of pregnancy on deep infiltrating endometriosis: serial ultrasound assessment of changes in size and pattern of deep endometriotic lesions.

BACKGROUND: Deep infiltrating endometriosis (DIE) is associated with severe painful symptoms and represents a complex management challenge. OBJECTIVE: To analyse the effect of pregnancy on deep infiltrating lesions and related symptomatology. STUDY DESIGN: As part of a longitudinal study performed over the past 3 years to determine the efficacy of hormonal treatment in treating women with DIE, we identified three cases of advanced pelvic endometriosis, all with DIE (deep recto-vaginal and recto-sigmoid involvement) where patients achieved spontaneous pregnancies. They were followed up by transvaginal ultrasound (TV-US). The main outcome measures were analysis of the size and echographic pattern of deep infiltrating lesions of endometriosis and evaluation of clinical symptoms during pregnancy. RESULTS: We observed modifications in lesion size and pattern. In the two patients observed in the third trimester, the lesions were more homogeneous with less evident limits of nodules and band-like echoes, less fibrotic-like. All patients showed complete resolution of symptoms during pregnancy. CONCLUSIONS: The hormonal environment produced by pregnancy might determine significant modifications of endometriotic lesions and reduce painful symptoms. As surgery for DIE is difficult, complex and can lead to major complications, the achievement of a pregnancy-specific hormonal state, through pregnancy or hormonal treatment, may be a valid option in selected cases.

Ovarian surgery for bilateral endometriomas influences age at menopause.

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.

Impact of endometriosis on in vitro fertilization and embryo transfer cycles in young women: a stage-dependent interference.

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.

Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain.

OBJECTIVE: To investigate factors that might influence the recurrence of both painful symptoms and endometriotic lesions following laparoscopic treatment of endometriosis. STUDY DESIGN: Retrospective cohort study in a University teaching hospital. We reviewed data from patients referred for laparoscopy between March 1993 and November 2007. We selected women who were followed up throughout Transvaginal-ultrasound (TV-US) after a first conservative laparoscopy for endometriosis. After laparoscopy, all patients were followed up according to an internal protocol: a standard gynaecologic examination, the assessment of painful symptoms and a TV-US scan that were repeated at 3, 6, and 12 months, and subsequently on a yearly basis. Sixteen factors were assessed by univariable and multivariable Cox proportional hazards models to evaluate their associations with recurrence of endometriotic lesions and pain related-endometriosis. RESULTS: 401 women were enrolled. A total of 154 (38.4%) experienced moderate or severe pain after laparoscopy; endometriotic lesions were observed by TV-US in 74 (18.4%) patients. In the multivariable model, age at menarche, severity of chronic pelvic pain (CPP) and dysmenorrhoea prior to surgery were significant risk factors for recurrence/occurrence of pain. Age at the first laparoscopy, stage of disease, pre-operative severity of CPP, and pregnancy were predictive factors of the recurrence for such lesions. CONCLUSION: The severity of CPP prior to the first laparoscopy showed the only significant factor in the overall prediction of recurrence of pain and endometriotic lesions. Patients with severe CPP at the time of their first surgery might represent a sub-group of women with a more aggressive form of endometriosis.

The worldwide frozen embryo reservoir: methodologies to achieve optimal results.

Cryopreservation of the human embryo has been successfully achieved at the zygote (day 1), cleavage (day 2/3), and blastocyst (day 5) stages; however, each stage presents specific advantages and disadvantages. During the past decades, two major methods have been applied: slow freezing (equilibrium procedure) and vitrification (nonequilibrium procedure). The overwhelming majority of published data prove that the latest vitrification methods induce less cellular trauma and are a more effective cryopreservation technique of human embryos than any other versions of slow freezing. For this reason, fragmented and slow-cleaving embryos that normally would not be recommended may be revaluated for cryopreservation by using the vitrification method. Furthermore, if laser-assisted necrotic blastomere removal is associated with the slow-freezing/thawing procedure, good clinical results can be obtained. Finally, the most proper embryo cleavage stage at which to perform cryopreservation has to be assessed according to clinical indications and laboratory experience.

Intensive care treatment of ovarian hyperstimulation syndrome (OHSS).

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.

The artificial womb.

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.

Intracytoplasmic injection of morphologically selected spermatozoa (IMSI) improves outcome after assisted reproduction by deselecting physiologically poor quality spermatozoa.

PURPOSE: We used computer assisted sperm selection (MSOME) during cycles of intracytoplasmic sperm injection to test whether this technique improves results over traditional ICSI protocols. We also used the TUNEL assay to test whether MSOME could deselect physiologically abnormal spermatozoa. METHODS: Individual spermatozoa were examined with MSOME. Normal and abnormal spermatozoa were tested for the level of DNA fragmentation using TUNEL assay. In a prospective, randomized trial, patients were selected for standard ICSI, or IMSI techniques. We tested the two groups for biological and clinical parameters. RESULTS: 64.8% of spermatozoa, otherwise selectable for ICSI, were characterized by abnormalities after computer-assisted sperm analysis. These sperm were also characterized by an increase in the level of DNA fragmentation. We noted an increase in embryo quality, pregnancy and implantation rates after computerized sperm selection during ICSI procedures. CONCLUSIONS: Computerised selection of spermatozoa during ICSI procedures deselects physiological abnormal spermatozoa and improves clinical results.

Vaginal parturition decreases recurrence of endometriosis.

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.