Two successful spontaneous pregnancies, single and twin, in uterus bicornis unicollis after deep infiltration endometriosis surgery.

A 26-year-old patient was admitted in our center with one year of infertility history after a miscarriage. She was diagnosed with uterus bicornis unicollis and deep infiltrating endometriosis (DIE); therefore, she underwent endometriosis focus removal surgery. After six-months, she conceived spontaneously and delivered one healthy baby. One year after the first pregnancy delivery, she conceived spontaneously and delivered twins in an extremely rare condition of uterus bicornis unicollis, of which there are only 15 cases reported worldwide. Both pregnancies were monitored every two or three weeks using ultrasonography to assess fetal growth, and cervical length was measured to assess the risk of premature delivery.

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.

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.

Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women.

Embryo implantation failure and recurrent abortion are common indications for endometrial evaluation to determine the implantation window and diagnose endometrial anomalies. There are few research studies comparing the efficacy of different techniques used for endometrial sampling in infertile females during the luteal phase. Likewise, morphometric studies of the endometrium through aspiration biopsy are scant. A cross-sectional study of 30 infertile and 10 fertile females was carried out. The study participants underwent hysteroscopic and aspiration biopsies (pipelle) at the midluteal phase. Computer-assisted morphometric and pathological anatomy analyses were conducted independently by two pathologists blinded to the study. The two endometrial sampling biopsy techniques were compared through morphometric and pathological anatomy analyses using three parameters: a) the amount of material collected for the endometrial studies; b) the scope and origin of sampled materials; and c) the quality of the sample. Both biopsy techniques produced sufficient material for analysis. The directed biopsies yielded higher quality samples from targeted segments of the uterine cavity because samples were homogeneous and had no architectural distortion (p<0.05). Blood was present only in the samples obtained through a Pipelle. Endometritis was detected in 10% of the infertile women. Our findings suggest that hysteroscopic biopsies are superior to blinded aspiration biopsies.

Successful Live Birth in a Woman With 17α-Hydroxylase Deficiency Through IVF Frozen-Thawed Embryo Transfer.

CONTEXT: Congenital adrenal hyperplasia (CAH) due to 17α-hydroxylase deficiency in 46,XX patients is characterized by primary amenorrhea, absent or incomplete sexual maturation, infertility, low serum levels of estradiol, and elevated progesterone (P). There were no previous reports of singleton live births from such women. OBJECTIVE: To describe the first successful singleton live birth in a female with CAH due to 17α-hydroxylase deficiency. CASE DESCRIPTION: A 26-year-old Brazilian woman with CAH associated with 17α-hydroxylase deficiency due to the compound heterozygote mutation (p.W406R/P428L) in the CYP17A1 gene expressed the desire to conceive. In vitro fertilization (IVF) was recommended due to the complexity of the disorder. The first attempt of treatment failed despite the production of viable embryos. At the second IVF attempt, all viable embryos were frozen due to inadequate endometrial development associated with prematurely elevated serum P during ovarian stimulation. Subsequently, a long-acting GnRH agonist and oral dexamethasone were used to lower ovarian and adrenal P overproduction. Once serum levels of P were < 1 ng/mL, endometrial preparation with estradiol valerate and frozen-thawed embryo transfer were performed, resulting in a singleton pregnancy. Estradiol supplementation was completely suspended by 14 weeks of gestation. She delivered at 30 weeks and 4 days due to acute fetal distress. The puerperium was uneventful; the newborn was discharged in good conditions 5 weeks after birth. CONCLUSION: A successful live birth was achieved in a woman with 17-hydroxylase deficiency through IVF, cryopreservation of all embryos, and frozen-thawed embryo transfer after adequate endometrial preparation.

The relationship among HOXA10, estrogen receptor α, progesterone receptor, and progesterone receptor B proteins in rectosigmoid endometriosis: a tissue microarray study.

BACKGROUND: Very few studies have evaluated the expression of homeobox A10 (HOXA10) and steroid (estrogen and progesterone) receptors exclusively in deep endometriosis. Conclusions drawn from studies evaluating peritoneal and ovarian endometriosis are usually generalized to explain the pathogenesis of the disease as a whole. We aimed to evaluate the expression of HOXA10, estrogen receptor α (ER-α), progesterone receptor (PR), and PR-B in rectosigmoid endometriosis (RE), a typical model of deep disease. METHODS: We used RE samples from 18 consecutive patients to construct tissue microarray blocks. Nine patients each were operated during the proliferative and secretory phases of the menstrual cycle. We quantified the expressions of proteins by immunohistochemistry using the modified Allred score. RESULT: The HOXA10 was expressed in the stroma of nodules during the secretory phase in 5 of the 18 patients. Expression of ER-α (in 16 of 18 patients), PR (in 17 of 18 patients), and PR-B (17 of 18 patients) was moderate to strong in the glands and stroma of nodules during both phases. Expression of both PR (P = .023) and PR-B (P = .024) was significantly greater during the secretory phase. CONCLUSION: The HOXA10 is expressed in RE, where it likely imparts the de novo identity of endometriotic lesions. The ER-α, PR, and PR-B are strongly expressed in RE, which differs from previous studies investigating peritoneal and ovarian lesions. This suggests different routes of pathogenesis for each of the 3 types of endometriosis.

O cuidado psicológico ao médico em reprodução assistida: um enquadre diferenciado / Psychological care for the human reproduction physician: a distinct clinical setting

Profissionais da área da saúde entram em contato com o sofrimento humano mesmo quando não trabalham diretamente no campo da Psicologia. Este estudo baseou-se no referencial da psicanálise com vistas a compreender os aspectos do sofrimento humano que emerge para os médicos no exercício da reprodução assistida, e a importância do estudo do imaginário coletivo sobre situações de difícil manejo em suas clínicas. Participaram vinte e dois médicos que atuam em hospitais e clínicas do estado de São Paulo em âmbitos público e privado, independentemente de sexo, idade e tempo de formação. Foi utilizado o procedimento desenhos-estórias com tema, compreendido como procedimento dialógico. A entrevista caracterizou-se como uma situação especial de comunicação e expressão das emoções geradas nos atendimentos relacionados à temática proposta. Constatou-se a necessidade de proposição de espaços facilitadores da expressão emocional, que promovem a continência do sofrimento humano e a ocorrência de experiências reflexivo-vivenciais transformadoras do real.(AU)

Health professionals have to deal with human suffering, even if they don't deal directly with interventions in the psychology area. This study was based on Psychoanalysis, with the aim of understanding the aspects of human suffering which emerge with doctors in the exercise of their work with assisted human reproduction, considering the collective model concerning the difficult situations that they have to deal with in their clinics. Twenty-two doctors working in hospitals and clinics in the state of São Paulo, in both private and public facilities, volunteered to participate, ignoring sex, age and time since graduation. The Drawing and Storytelling thematic was used as the dialogical procedure. The interview was characterized as a special situation with the expression and communication of emotions generated in sessions related to the proposed theme. It was found that there was a need for the proposition of facilitating spaces for emotional expression, promoting the containment of human suffering and the occurrence of the transforming life reflection experiences of reality.(AU)

O cuidado psicológico ao médico em reprodução assistida: um enquadre diferenciado / Psychological care for the human reproduction physician: a distinct clinical setting

Profissionais da área da saúde entram em contato com o sofrimento humano mesmo quando não trabalham diretamente no campo da Psicologia. Este estudo baseou-se no referencial da psicanálise com vistas a compreender os aspectos do sofrimento humano que emerge para os médicos no exercício da reprodução assistida, e a importância do estudo do imaginário coletivo sobre situações de difícil manejo em suas clínicas. Participaram vinte e dois médicos que atuam em hospitais e clínicas do estado de São Paulo em âmbitos público e privado, independentemente de sexo, idade e tempo de formação. Foi utilizado o procedimento desenhos-estórias com tema, compreendido como procedimento dialógico. A entrevista caracterizou-se como uma situação especial de comunicação e expressão das emoções geradas nos atendimentos relacionados à temática proposta. Constatou-se a necessidade de proposição de espaços facilitadores da expressão emocional, que promovem a continência do sofrimento humano e a ocorrência de experiências reflexivo-vivenciais transformadoras do real.

Health professionals have to deal with human suffering, even if they don't deal directly with interventions in the psychology area. This study was based on Psychoanalysis, with the aim of understanding the aspects of human suffering which emerge with doctors in the exercise of their work with assisted human reproduction, considering the collective model concerning the difficult situations that they have to deal with in their clinics. Twenty-two doctors working in hospitals and clinics in the state of São Paulo, in both private and public facilities, volunteered to participate, ignoring sex, age and time since graduation. The Drawing and Storytelling thematic was used as the dialogical procedure. The interview was characterized as a special situation with the expression and communication of emotions generated in sessions related to the proposed theme. It was found that there was a need for the proposition of facilitating spaces for emotional expression, promoting the containment of human suffering and the occurrence of the transforming life reflection experiences of reality.

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.

Successful interval laparoscopic transabdominal cervicoisthmic cerclage preceding twin gestation: a case report.

Laparoscopic transabdominal cervicoisthmic cerclage (LTCC) is an alternative, less-morbid option to the traditional transabdominal cerclage, indicated for patients with cervical incompetence. Experience with the technique is based on case reports and a few case series. Considering LTCC for twin gestations, reports are very scarce and are derived from LTCC performed during pregnancy. We report the case of a 36-year-old patient, gravida 1, para 0, aborta 1, who underwent interval LTCC after a previous failed transvaginal emergency cerclage performed in the second trimester. Hysteroscopic metroplasty was concomitantly performed for an incomplete septate uterus. The procedure lasted 100 minutes, with an estimated blood loss of 50 mL. The patient was discharged home on the second postoperative day. The patient became pregnant with twins 3 months after the procedure after undergoing in vitro fertilization. The gestational course was uneventful, and the patient delivered 2 healthy neonates at 38 weeks gestation by elective cesarean section. The cerclage tape was left in situ. Minor modifications of the previously reported techniques included use of a laparoscopic Deschamps needle for placing the cotton cardiac tape used as suture material. Vessels in the cervical transverse cervical ligament were exposed before cerclage tape application. To our knowledge, this is the first report of interval LTCC preceding a twin gestation.

Should the gynecologist perform laparoscopic bowel resection to treat endometriosis? Results over 7 years in 168 patients.

STUDY OBJECTIVE: To assess the feasibility and safety of laparoscopic bowel resections for endometriosis performed by gynecologic surgeons. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-3). SETTING: Fertility and pelvic surgery clinics. PATIENTS: One hundred sixty-eight women (age 21-53 years) with symptoms including pelvic pain, infertility, or both with 252 bowel endometriotic lesions underwent laparoscopic bowel resection performed by gynecologic surgeons between May 2000 and January 2008. INTERVENTIONS: Laparoscopic procedures for excision of several endometriotic nodes and lesions included shaving resection (LscShR), discoid resection (LscDR), segmental resection (LscSgR), terminal ileal resection (LscIR), partial cecal resection (LscCR), and appendectomy (LscAp). MEASUREMENTS AND MAIN RESULTS: The 168 patients underwent 172 laparoscopic bowel resections (4 patients were operated on twice) by the same surgeon. Lesions were distributed as follows: 133 (79%) in the rectum, 61 (24%) in the sigmoid colon, 47 (19%) in the appendix, 5 (2%) in the terminal ileum, 3 (1%) in the descending colon, and 3 (1%) in the cecum. At surgeon discretion, 12 lesions were not resected. A total of 216 bowel procedures were necessary to remove the 240 lesions include shaving resection in 22 patients (10%), discoid resection in 52 (24%), segmental resection in 92 (42%), terminal ileal resection in 2 (1%), partial cecal resection in 1 (0.6), and appendectomy in 47 (22%). Major complications occurred in 13 patients (7.6%) and included rectovaginal fistula in 3 patients (1.7%), rectosigmoid anastomosis dehiscence and bowel occlusion in 1 patient each (0.6%), and persistent bowel dysfunction in 4 patients (2.3%). These results are comparable to those reported in the literature to date. Complete relief of symptoms (measured using the Visick scale) was noted in patients with dysmenorrhea (59%), dyspareunia (75%), noncyclic pelvic pain (90%), pain on defecation (100%), constipation (83%), and cyclic rectal bleeding (100%). CONCLUSION: Surgery to treat bowel endometriosis can be safely and efficiently performed by the gynecologic pelvic surgeon. Meticulous training and a multidisciplinary approach to comprehensive operative care are necessary. These findings can be validated by prospective collaborative studies and reports from other surgeons.

Células natural killer endometriais: o que são? O que fazem? O que devemos saber? / Endometrial natural killer cells: what are they? What do they do? What do we need to know?

As células natural killer endometriais, também chamadas células natural killer uterinas, têm recebido especial atenção no campo da imunologia reprodutiva. Teorias que consideram alterações na resposta imune como uma causa de infertilidade conjugal e de falhas nos tratamentos de reprodução assistida têm ponderado um possível envolvimento negativo das células natural killer endometriais. As células natural killer são linfócitos que podem ser identificados no sangue periférico e no endométrio, apresentando diferenças fenotípicas e funcionais importantes. As células periféricas não se alteram com a fase do ciclo menstrual e implantação, sendo que as células natural killer endometriais apresentam variações durante o ciclo menstrual e período peri-implantacional, com menores concentrações durante a fase proliferativa e aumentando na segunda fase do ciclo. A célula natural killer endometriais participam nas várias fases da implantação, invasão trofoblástica, placentação e desenvolvimento fetal e no desenvolvimento da gestação humana até aproximadamente 20 semanas.

Endometrial natural killer cells have been given special attention in reproductive immunology. The relation between the endometrial natural killer cells and alterations in the immune response as a cause of couples infertility and failure in assisted reproduction treatment have been studied in several theories. Natural killer cells are lymphocytes that may be identified in peripheral blood and endometrium, with phenotypical and functional differences between them. Peripheral natural killer cells do not change with the menstrual cycle or implantation, as opposed to endometrial natural killer cells which present lower concentration in the proliferative phase and higher concentration in the luteal phase. Endometrial natural killer cells play an important role in the implantation, trophoblastic invasion, placentation, fetal development and development of the human pregnancies up to 20 weeks of gestation.

Effect of GnRH down-regulation on cumulus cell viability and apoptosis as measured by fluorescence-activated cell sorting.

OBJECTIVE: To determine whether gonadotropin releasing hormone (GnRH)-agonist or -antagonist induces higher percentages of cumulus cell apoptosis and if the use of either is detrimental to ART outcomes. PATIENTS: Women in a private facility under treatment for IVF had their cumulus cells isolated and analyzed by flow cytometry. Viable, apoptotic, and dead cumulus cell rates related to ovarian stimulation by GnRH-agonist or -antagonist were measured and compared with fertilization and implantation rates. RESULTS: Treatment with GnRH-agonist produced a greater number of follicles than treatment with GnRH-antagonist. No differences in implantation and pregnancy rates were found. While cumulus cell (CC) apoptosis was positively correlated with estradiol on the day of hCG administration, no significant difference in the percentage of apoptotic cells between treatments was detectable. Additionally, implantation rate and the average follicular estradiol production on the day of hCG administration were no different between treatments. CONCLUSIONS: GnRH-agonist or -antagonist treatment protocols induce similar levels of apoptosis in CCs and are not detrimental to ART outcomes.

Expressão protéica no endométrio durante a fase lútea do ciclo menstrual / Endometrial protein expression during the luteal phase of the menstrual cycle

Introdução: O objetivo foi avaliar a expressão de algumas proteínas no endométrio durante a fase lútea do ciclo menstrual de mulheres férteis e inférteis, por meio imunoistoquímica de micro-arranjos teciduais (TMA). Métodos: Analisou-se a expressão de dez proteínas em 52 amostras de endométrio obtidas nas fases lútea inicial, intermediária (janela de implantação) e final. Resultados: As proteínas, fator inibidor de leucemia (LIF), fator de crescimento insulinóide tipo 1 (IGF-1), receptor de progesterona (PR), claudina-4, receptor de fator de crescimento vascular endotelial 3 (VEGFR-3) e citoqueratina 7 (CK-7) mostraram-se expressas no endométrio nas fases lútea inicial, intermediária e final. A proteína morfogenética óssea 4 (BMP-4) expressou-se no endométrio nas fases lútea inicial e intermediária. As proteínas citoqueratina 17 (CK-17), substância solúvel 100 (S100) e calretinina não se expressaram no endométrio durante os três períodos avaliados. Houve correlação entre as expressões protéicas de LIF, IGF-1 e PR. As proteínas LIF e BMP-4 foram diferencialmente expressos no endométrio nas fases lútea inicial, intermediária e final. As proteínas claudina-4 e PR não se expressam simultâneamente no endométrio durante a fase lútea. Conclusão: Baseados nos resultados deste estudo podemos sugerir que a presença das proteínas LIF, IGF-1 e PR durante a janela implantacional teria relevância como preditor do adequado desenvolvimento do endométrio.

Introduction: The objective of this study was to evaluate endometrial protein expressions from fertile and infertile women during the luteal phase of the menstrual cycle by immunohistochemistry in tissue microarrays (TMA). Method: The expression of ten proteins obtained from 52 endometrial samples in the initial, mid (window of implantation) and late (premenstrual) phases of the menstrual cycle were evaluated. Results: The proteins leukemia inhibitory factor (LIF), insulin like growth factor 1 (IGF-1), progesterone receptor (PR), claudin-4, vascular endothelial growth factor receptor 3 (VEGFR-3), and cytokeratin 7 (CK-7) were expressed in the endometrium in the three intervals of the luteal phase. Endometrial expression of the morphogenetic bone protein 4 (BMP-4) occurred during the initial and mid luteal phases. Cytokeratin 17, substance 100 and calretinin were not expressed in the luteal phase. There were positive correlations among endometrial expressions of LIF, IGF- 1, and PR. LIF and BMP-4 were differently expressed in the initial, mid and late phases of the luteal phase. Claudin-4 and PR did not express simultaneously during the different intervals of the luteal phase. Conclusion: These findings suggest that positively correlated endometrial expressions of LIF, IGF-1 and PR at the window of implantation could characterize an adequately developed and receptive endometrium.