Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility.

BACKGROUND: Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia. METHODS: In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts. FINDINGS: The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. Immunosuppression was induced with prednisolone and thymoglobulin and continued via tacrolimus and mycophenalate mofetil (MMF), until 5 months post-transplantation, at which time azathioprine replaced MMF. First menstruation occurred 37 days post-transplantation, and regularly (every 26-32 days) thereafter. Pregnancy occurred after the first single embryo transfer 7 months post-transplantation. No blood flow velocity waveform abnormalities were detected by Doppler ultrasound of uterine arteries, fetal umbilical, or middle cerebral arteries, nor any fetal growth impairments during pregnancy. No rejection episodes occurred after transplantation or during gestation. Caesarean delivery occurred on Dec 15, 2017, near gestational week 36. The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended. INTERPRETATION: We describe, to our knowledge, the first case worldwide of livebirth following uterine transplantation from a deceased donor in a patient with MRKH syndrome. The results establish proof-of-concept for treating uterine infertility by transplantation from a deceased donor, opening a path to healthy pregnancy for all women with uterine factor infertility, without need of living donors or live donor surgery. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo and Hospital das Clínicas, University of São Paulo, Brazil.

Human endometrial stromal cells inhibit the pro-angiogenic stimulus of hCG in vitro.

During embryo implantation, endometrial angiogenesis is regulated by signals originating from the endometrium itself and the developing embryo. It has been suggested that hCG may play a pro-angiogenic role; therefore, we sought to understand its regulatory role in blood vessel formation in human endometrium using in vivo and in vitro models. In the in vivo model, we screened 16 angiogenesis-related transcripts in the endometrium upon intrauterine administration of hCG. Oocyte donors were recruited and during their controlled ovarian stimulation cycle received a single dose of hCG or vehicle on the day of oocyte pick up during a cycle of ovarian stimulation. One hour before obtaining an endometrial sample, women received an intrauterine administration of vehicle or hCG (500, 1500 and 5000 IU). Transcript and protein analysis showed that MMP3 and VEGFA increased, whereas TIMP1 decreased. The in vitro analysis studied the angiogenic potential of conditioned medium (CM) from primary cultures of human endometrial stromal cells (ESC) stimulated with hCG. Using a 2D and 3D in vitro angiogenesis assays, our results indicate that CM from ESC almost completely inhibits the capillary-like structure formation in endothelial cells, overriding the pro-angiogenic effect of hCG; and this inhibition due to secreted factors present in CM specifically reduced the migration potential of endothelial cells. In conclusion, the endometrial stromal milieu seems to modulate the direct pro-angiogenic effects of hCG on endothelial cells during embryo implantation.

Analysis of hyaluronic acid in the endometrium of women with polycystic ovary syndrome.

Endometrium extracellular matrix provides a wide range of signals at different cellular levels, like cell death and proliferation, which can be important for regulating menses and reducing the proliferative processes. The objective of this study is to evaluate hyaluronic acid concentration, the enzymes of hyaluronic acid synthases in the endometrium of patients with polycystic ovary syndrome (PCOS) and eumenorrheic women. A total of 60 endometrial samples from 30 patients with PCOS and 30 women with regular menstrual cycles in the proliferative phase, attended at Gynecology Division of Clinical Hospital of the FMUSP (HC-USP). Profile determination and the concentration of hyaluronic acid was performed by the biochemical method of the fluorimetric assay (ELISA-like). Its location in the endometrial tissue as well as the dosage of enzymes synthases (HAS1, HAS2 and HAS3) was done by immunohistochemistry and western blotting. Statistical analyses were performed with one-way ANOVA, followed by the Bonferroni test. Regarding hyaluronic acid synthases, there was a higher HAS1 and HAS2 reactivity and lower HAS3 reactivity in the PCOS endometrium compared to women with regular menstrual cycles in the proliferative phase. We suggest that PCOS patients have different composition of hyaluronic acid in relation to a regular cycle in the proliferative phase.

Risk factors for inadequate response to ovarian stimulation in assisted reproduction cycles: systematic review.

PURPOSE: Controlled ovarian stimulation is a fundamental part of a successful assisted reproduction treatment, and recognizing patients at risk of a poor response allows the development of targeted research to propose new treatment strategies for this specific group. The objective of this systematic review was to determine risk factors for poor ovarian response (POR) to controlled stimulation in assisted reproduction cycles described in the literature. METHODS: The primary databases MEDLINE, Cochrane, LILACS, and SciELO were consulted, using specific terms with a restriction for articles in English or Portuguese published in the last 10 years. RESULTS AND CONCLUSION: Our data suggest that environmental endocrine disruptors, tobacco, genetic mutations, endometriomas, ovarian surgery, chemotherapy, and short menstrual cycles are factors that influence stimulation in assisted reproduction cycles. Further studies are necessary for characterizing patients with prior risk factors.

Ovarian reserve in young juvenile idiopathic arthritis patients.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. RESULTS: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

Translabial US and Dynamic MR Imaging of the Pelvic Floor: Normal Anatomy and Dysfunction.

Pelvic floor dysfunction (PFD) is a common condition that typically affects women older than 50 years and decreases the quality of life. Weakening of support structures can involve all three pelvic compartments and cause a combination of symptoms, including constipation, urinary and fecal incontinence, obstructed defecation, pelvic pain, perineal bulging, and sexual dysfunction. The causes of PFD are complex and multifactorial; however, vaginal delivery is considered a major predisposing factor. Physical examination alone is limited in the evaluation of PFD; it frequently leads to an underestimation of the involved compartments. Imaging has an important role in the clinical evaluation, yielding invaluable information for patient counseling and surgical planning. Three- and four-dimensional translabial ultrasonography (US) is a relatively new imaging modality with high accuracy in the evaluation of PFD such as urinary incontinence, pelvic organ prolapse, and puborectalis avulsion. Evaluation of mesh implants is another important indication for this modality. Dynamic magnetic resonance (MR) imaging of the pelvic floor is a well-established modality for pelvic floor evaluation, with high-resolution images yielding detailed anatomic information and dynamic sequences yielding functional data. Specific protocols and dedicated image interpretation are required with both of these imaging methods. In this article, the authors review the normal anatomy of the female pelvic floor by using a practical approach, discuss the roles of translabial US and MR imaging in the investigation of PFD, describe the most appropriate imaging protocols, and illustrate the most common imaging findings of PFD in the anterior, middle, and posterior compartments of the pelvis. Online supplemental material is available for this article. ©RSNA, 2018.

Atypical Sites of Deeply Infiltrative Endometriosis: Clinical Characteristics and Imaging Findings.

Endometriosis is defined as the presence of endometrial tissue that is located outside the uterine cavity and associated with fibrosis and inflammatory reaction. It is a polymorphic and multifocal disease with no known cure or preventive mechanisms. Patients may be asymptomatic or may experience chronic pelvic pain, dysmenorrhea, dyspareunia, or infertility. The pelvic cavity is the most common location for endometriotic implants, which usually affect the retrocervical space, ovaries, vagina, rectosigmoid colon, bladder dome, and round ligaments. Atypical endometriosis is rare and difficult to diagnose. The most common atypical locations are the gastrointestinal tract, urinary tract, lung, umbilicus, inguinal area, breast, and pelvic nerves, as well as abdominal surgical scars. Gastrointestinal lesions are the most common extragenital manifestation, and the diaphragm is the most frequent extrapelvic site. The catamenial nature of the symptoms (occurring between 24 hours before and 72 hours after the onset of menstruation) may help suggest the diagnosis, but imaging by specialists is fundamental to evaluation. Depending on the area affected, radiography, ultrasonography, thin-section computed tomography, or magnetic resonance imaging can be used to assess suspected lesions. Because isolated extragenital endometriosis is rare, concomitant evaluation of the pelvic cavity is mandatory. Surgical excision is the only therapeutic option for definitive treatment, and comprehensive disease mapping is necessary to avoid residual disease. The authors review atypical locations for endometriosis and emphasize the most appropriate imaging protocols for investigation of various clinical manifestations. Online supplemental material is available for this article. ©RSNA, 2018.

Psychosocial benefits of fertility preservation for young cancer patients.

PURPOSE: The risk of ovarian failure after radiotherapy and/or chemotherapy is a concern among oncologic women. There is no doubt regarding the psycho-emotional benefits of fertility preservation (FP) after a cancer diagnosis because concerns about biological conception are a source of anxiety and can even affect the patient's cancer recovery. The aim of this study was to evaluate oncology patients' feelings, concerns, and life quality impacts related to FP. METHODS: This qualitative cross-sectional study was based on a questionnaire administered to a selected group of women diagnosed with cancer who underwent FP. Thirty-four eligible women (23-39 years old) completed this questionnaire. RESULTS: Two of the participants already had a child, and most of them (61.8%) stated a desire to have children at the time of FP. Their feelings primarily involved safety (44.1%) and hope (23.5%). Time and/or financial issues (82.4%) were the main challenge for FP. All of the women noted the importance of FP, with many stating that it is warranted to allow the possibility of a biological pregnancy due to the risk of infertility. Finally, questions about the impact on their lives if they had not undergone FP indicated emotional impairment, low quality of life, relationship problems, and uncertainty about maternity. CONCLUSIONS: FP for oncology patients is a positive strategy. The women in this study felt that FP was a worthwhile process and that the security of having undergone FP brought them peace during oncological treatment and contributed to their quality of life.

Egg donation of vitrified oocytes bank produces similar pregnancy rates by blastocyst transfer when compared to fresh cycle.

PURPOSE: Advances in reproductive techniques, mainly the introduction of oocyte vitrification, have provided the opportunity to conceive from oocyte banks. The aim of this study was to compare the clinical outcomes of fresh and vitrified oocytes in an egg donation program following blastocyst transfer. METHODS: This retrospective observational study included 504 oocyte donation cycles. All donor women were younger than 30 years of age. The recipient cycles were divided into two groups: fresh oocytes (n = 78) or vitrified oocytes (n = 426). All oocytes were fertilized by ICSI using ejaculated sperm, followed by blastocyst transfer. Endometrium preparation was performed with estradiol valerate plus micronized progesterone according to standard protocols. RESULTS: Recipients were of similar age (fresh 42.0 ± 4.5 years vs vitrified 41.8 ± 4.8 years; p = 0.790). The fresh group received more mature oocytes for injection compared to the vitrified group (10.1 ± 2.8 vs 9.2 ± 2.2; p = 0.005). The two pronuclei (2PN) rate (74.5 vs 77.4%; p = 0.195) and blastocyst rate (48.8 vs 51.6%; 0.329) were similar between the fresh and vitrified groups, respectively. The rates of clinical pregnancy were 60.9% in the fresh and 59.0% in the vitrified groups (p = 0.771). CONCLUSIONS: Our findings suggest that vitrified oocytes result in similar pregnancy rates when compared to fresh oocytes with blastocyst transfer in an egg donation program. Moreover, vitrified oocytes may allow for a better cycle schedule, starting with a lower number of oocytes to be fertilized. Therefore, we hypothesize that egg banks with vitrified oocytes could be safely utilized in an egg donation program.

Positive rheotaxis extended drop: a one-step procedure to select and recover sperm with mature chromatin for intracytoplasmic sperm injection.

PURPOSE: The purpose of this study was to develop a novel one-step ICSI approach to select sperm with better chromatin maturity than the conventional method. METHODS: This was a pilot diagnostic study, which prospectively recruited men during a 6-month period in a University-affiliated infertility centre. Forty consecutive semen samples were provided for analysis. The positive rheotaxis extended drop (PRED) was set up creating a pressure and viscosity gradient. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), two aliquots for PRED (fresh semen (PRED-FS) and processed semen (PRED-DGC)), and one aliquot as the control (FS). In PRED, a mean of 200 spermatozoa were collected consecutively without selection from the outlet reservoir. The aniline blue assay was used to assess chromatin immaturity. RESULTS: The mean channel length, measured from inlet to outlet, was 32.55 ± 0.86 mm, with a mean width of 1.04 ± 0.21 mm. In 82.5% of cases (33/40), at least 50 spermatozoa were captured between 15 and 30 min. Improved chromatin maturity after the DGC preparation and the PRED approach was observed in all samples. This was reflected by a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC and 0.89 ± 1.31% in the PRED approach (P < 0.01). CONCLUSIONS: The PRED method may improve the current ICSI technique by providing it with its own sperm selection process. ICSI would probably become an even more complete technique comprising selection, capture and injection of the male gamete.

Does slow embryo development predict a high aneuploidy rate on trophectoderm biopsy?

The aneuploidy rates in expanded blastocysts biopsied on days 5 and 6 development were assessed in women undergoing IVF followed by array comparative genomic hybridization. This study included 1171 expanded blastocysts from 465 patients. Among the 465 patients, 215 and 141 underwent embryo biopsy on day 5 and day 6 (46.2% and 30.3%, respectively), and 109 underwent biopsy on both days 5 and 6 (23.4%). The cycles of 206 women were cancelled because only aneuploidy embryos were present (44.3%). The aneuploid embryos were classified according to the type as single, double or complex aneuploidy. No differences were observed in the distributions of these three categories according to the day of the biopsy. The aneuploidy rate was also evaluated according to maternal age, and was found to be higher in older patients; however, no differences in this rate were detected between embryos biopsied on days 5 and 6 according to maternal age. Biopsy was carried out when blastocysts reached the expanded stage. The embryos biopsied on day 6 had a higher rate of aneuploidy (69.9%) than those biopsied on day 5 (61.4%); however, the euploid embryos transferred had similar chances for successful and healthy gestation.

Outcomes of elective cryopreserved single or double embryo transfers following failure to conceive after fresh single embryo transfer.

The main adverse effect of IVF is the high multiple pregnancy rate resulting from the transfer of two or more embryos. The objective was to evaluate pregnancy rates in infertile women with a good prognosis who failed to conceive in a fresh elective single embryo transfer (eSET) and had a second cycle with elective double vitrified-warmed embryo transfer (eDFET) compared with elective single vitrified-warmed embryo transfer (eSFET). A total of 142 intracytoplasmic sperm injection cycles using a conventional protocol were evaluated. Good-prognosis patients underwent eSET in a fresh cycle, and those who failed to conceive underwent a second vitrified-warmed embryo transfer: eDFET (n = 102) or eSFET (n = 40). Embryos were transferred and vitrified on day 5 of development. Patients who received eDFET had fewer implantations (30.9%) than eSFET (52.5%; P = 0.004); pregnancy rates were similar (eDFET: 35.3%, eSFET: 42.5%). Patients with the eSFET had one monozygotic twin (5.9%), and 22.2% of eDFET patients had multiple pregnancies. Patients with a good prognosis who failed to conceive in the first fresh eSET did not have an advantage when receiving eDFET in the second cycle, as pregnancy rates were similar; 22.2% of patients in the eDFET group had multiple pregnancies.

Expression of stem cell-related genes in the endometrium and endometriotic lesions: a pilot study.

OBJECTIVE: To compare the expression of stem cell-related genes in the endometrium (END), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE). STUDY DESIGN: We performed a prospective pilot study of six women suffering from SE and DIE who gave consent for laparoscopy surgery, endometrial biopsies, and participation in this study. Quantitative RT-PCR analysis of 84 stem cell-related genes was performed in 18 biopsy samples. RESULTS: A total of 40 of 84 genes were expressed in SE and DIE, but were different from END as follows. Seven genes were over-expressed in SE and 33 genes were under-expressed in DIE compared with END. Two genes were only over-expressed in SE and three genes were only over-expressed in DIE. Six under-expressed genes were exclusively located in SE and one was only located in DIE. The remaining 31 genes were not different among the groups. There was no significant difference in gene expression between SE and DIE samples. CONCLUSION: Tissue of DIE and SE appears to have similar stem cell-related genes. Nevertheless, there are differences in gene expression between SE and DIE.

Study of two strategies to induce follicular wave emergence for assisted reproductive treatments (ART)-a preliminary trial.

PURPOSE: This study aimed to induce follicular wave emergence (FWE) using pharmacological (recombinant hCG administration) or mechanical (aspiration of dominant follicle) interventions in infertile women. METHODS: Sixteen infertile women (≤35 years) with indications for in vitro fertilization due to tubal and/or male factor infertility were randomized into three groups: control (n = 6), pharmacological (n = 5) and mechanical (n = 5) groups. Women in both experimental groups underwent serial transvaginal sonograms (TVS) from menstrual cycle day 10 until identification of a dominant follicle ≥15 mm. Women in the pharmacological group received 250 µg of recombinant-hCG to induce ovulation, and resumed serial TVS 2 days later. In the mechanical group, dominant and subordinate follicles ≥10 mm were aspirated, and daily TVS was resumed on the following day. An increased pool of follicles ≥5 and ≤9 mm after interventions characterized FWE. Women in the control group underwent ovulation induction (OI) with 150 IU/day of recombinant follicle-stimulating hormone started on menstrual cycle day 3 (D3). OI was started on the day of FWE in the experimental groups. Endometrial asynchrony with development of the embryo was expected in the experimental groups. Therefore, all viable embryos were cryopreserved and transferred in an endometrial-stimulated cycle. RESULTS: The number of follicles ≥5 and ≤9 mm increased after the interventions in both experimental groups (p < .001), indicating induction of FWE. OI outcomes were similar among the groups. CONCLUSIONS: The pharmacological and mechanical interventions are efficient in inducing FWE; outcomes of OI synchronized with FWE should be further investigated.

The effects of bromocriptine on VEGF, kidney function and ovarian hyperstimulation syndrome in in vitro fertilization patients: a pilot study.

The aim of this study was to evaluate the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Twenty-eight women were randomly divided into two groups and were administered daily oral capsules for 14 days, starting on the day of human chorionic gonadotropin (hCG) administration. Group A received 2.0 mg of folic acid, whereas Group B was given 2.5 mg of bromocriptine. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and again 7 days later. No differences in ovarian hyperstimulation syndrome, urine volume, creatinine clearance, urine sodium concentration or serum VEGF levels were found between the two groups. Thus, these results indicate that bromocriptine does not affect blood levels of VEGF, kidney function or the incidence of ovarian hyperstimulation syndrome in high-risk patients subjected to in vitro fertilization.

Psycho-emotional acceptance in couple and single women who choose to undergo IVF treatment with donor eggs.

New family configurations are emerging concurrently with improved assisted reproduction techniques, including the use of donated gametes. Most indications for treatment when using donated eggs are caused by an age-related decrease in reproductive capacity. We evaluated the emotional state regarding accepting egg donation in participants who chose this option for in vitro fertilization cycles. This is a retrospective, Brazilian cohort study, based on data collected from sixty psychological counseling sessions with participants that opted to be enrolled in an egg donation program. A single professional conducted semi-structured psychological counselling sessions. The data were analyzed using a thematic analysis as the qualitative methodology. Two years after the psychological counseling sessions, participants were contacted to obtain information about their outcomes. Of 60 sessions, 19 (32%) were classified as involving participants with positive emotional state (group 1), 14 (23%) with unfavorable emotional state (group 2), and 27 (45%) without evident classification (group 3). Three couples did not undergo treatment until two years after the psychological counselling session and the other couples underwent treatment in a period ranging from 1-8 months after the session. This is the first study in the Brazilian population regarding the acceptance of egg donation. The process of acceptance of infertility and the impossibility to have a biological child is fundamental to gradually accepting a new way of becoming a parent. Psychological counseling can contribute to reflecting on the use of donated eggs, exploring its emotional implications and identifying the need for psychotherapeutic work to address conflict and suffering.

MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.

MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.

Theoretical and experimental basis of oocyte vitrification.

In the last decades significant advances have been made in successful cryopreservation of mammalian oocytes. Human oocyte cryopreservation has practical application in preserving fertility for individuals at risk of compromised egg quality due to cancer treatments or advanced maternal age. While oocyte cryopreservation success has increased over time, there is still room for improvement. Oocytes are susceptible to cryodamage; which collectively entails cellular damage caused by mechanical, chemical or thermal forces during the vitrification and warming process. This review will delineate many of the oocyte intracellular and extracellular structures that are/may be stressed and/or compromised during cryopreservation. This will be followed by a discussion of the theoretical basis of oocyte vitrification and warming, and a non-exhaustive review of current experimental data and clinical expectations of oocyte vitrification will be presented. Finally, a forward-thinking vision of a potential means of modifying and improving vitrification and warming procedures and success will be proposed. This review addresses theoretical and experimental evidence accumulated over the last two decades supporting the application of vitrification and warming to oocyte cryopreservation. Issues ranging from clinical needs for oocyte cryopreservation, cryopreservation-induced stresses and normal oocyte function, practical application of vitrification-warming of oocytes, and potential future directions will be discussed. In addition, we debate commonly discussed technical methods of oocyte vitrification-warming that may not necessarily be grounded in scientific knowledge. Instead these methodologies are many times theoretical, potentially empirical and commonly lack significant testing and scientific rigor. Questions include: (i) what is the best cryoprotectant? (ii) are some cryoprotectants more toxic compared with others? (iii) how should cryosolutions be mixed with cells? (iv) is there a best container for vitrification? (v) is there a threshold cooling-warming rate or is a faster rate always better? and finally (vi) should oocytes be vitrified with or without adjacent cells? With this said, it is recognized that important advancements have been made in the past decade in oocyte cryopreservation, many times through empirical findings. Finally, we propose some new areas of research that may influence future success of oocyte vitrification and warming, fully recognizing that these theories require mechanical and biological experimental testing.

Findings of pelvic endometriosis at transvaginal US, MR imaging, and laparoscopy.

Endometriosis is a common multifocal gynecologic disease that manifests during the reproductive years, often causing chronic pelvic pain and infertility. It may occur as invasive peritoneal fibrotic nodules and adhesions or as ovarian cysts with hemorrhagic content. Although findings at physical examination may be suggestive, imaging is necessary for definitive diagnosis, patient counseling, and treatment planning. The imaging techniques that are most useful for preoperative disease mapping are transvaginal ultrasonography (US) after bowel preparation, and magnetic resonance (MR) imaging. Initial transvaginal US is a reliable technique for detecting rectosigmoid endometriotic lesions. MR imaging is indicated as a complementary examination in complex cases of endometriosis with extensive adhesions and ureteral involvement. Peritoneal endometriotic implants are typically hypoechoic on transvaginal US images and demonstrate low signal intensity on T2-weighted MR images. Endometriotic implants most commonly are found in retrocervical and rectosigmoid sites, followed by the vagina, bladder, and ureters. Cysts with low-level internal echoes and echogenic peripheral foci at transvaginal US are suggestive of endometriomas. MR imaging has high specificity for identifying endometriomas, which are characterized by high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Correlation of the radiologic imaging features of endometriotic lesions with their laparoscopic appearances may help improve individual proficiency in the radiologic diagnosis of endometriosis.

Transvaginal US after bowel preparation for deeply infiltrating endometriosis: protocol, imaging appearances, and laparoscopic correlation.

Deeply infiltrating endometriosis (DIE) is a common gynecologic disease that is characterized by a difficult and delayed diagnosis. Radiologic mapping of the DIE lesion sites is crucial for case management, patient counseling, and surgical planning. Transvaginal ultrasonography (US) is the initial imaging modality for investigating DIE and has been the focus of several recent studies. DIE typically manifests at imaging as hypoechogenic nodules throughout the affected sites and thickening of the intestinal wall, with some lesions showing a mixed pattern due to cystic areas. Transvaginal US performed after bowel preparation improves the ability to diagnose intestinal lesions and provides invaluable details, including which layers of the intestine are affected and the distance between the lesion and the anal border. It is vital that radiologists be familiar with the technical aspects of this modality and with the US manifestations of DIE lesions. Transvaginal US performed after bowel preparation should be the first-line imaging modality for the evaluation of women with suspected endometriosis.