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.

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.

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.

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.

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.

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.

Tests for ovarian reserve: reliability and utility.

PURPOSE OF REVIEW: This review discusses ovarian reserve tests for ovulation induction and their application in determining fertility capacity, and their current applications to assess risk of natural ovarian failure and to estimate ovarian function after cancer treatment. RECENT FINDINGS: The current arsenal of ovarian reserve tests comprises hormonal markers [basal follicle stimulating hormone, estradiol, inhibin-B, antimullerian hormone (AMH)] and ultrasonographic markers [ovarian volume, antral follicle counts (AFCs)]. These markers have limitations in terms of which test(s) should be used to reliably predict ovarian reserve with regard to accuracy, invasiveness, cost, convenience, and utility. Several studies have correlated sonographic AFCs with serum AMH levels for predicting the ovarian response to ovulation induction protocols during assisted reproduction treatments. SUMMARY: Serum AMH levels and AFC are reliable tests for predicting the ovarian response to ovulation induction. However, none of the currently employed tests of ovarian reserve can reliably predict pregnancy after assisted conception. Further, ovarian reserve tests cannot predict the onset of reproductive and hormonal menopause; thus, they should be used with caution for reproductive life-programming counseling. Moreover, there is no evidence to support the use of ovarian reserve tests to estimate the risk of ovarian sufficiency after cancer treatments.

The feasibility of laparoscopic bowel resection performed by a gynaecologist to treat endometriosis.

PURPOSE OF REVIEW: Intestinal endometriosis is commonly diagnosed in the setting of deeply infiltrating endometriosis. A multidisciplinary team that includes gynaecologists and general surgeons traditionally performs laparoscopic bowel resections for symptomatic patients. Recently, Pereira et al. has published the results of a series of patients who underwent laparoscopic bowel resection for endometriosis performed by a team of gynaecologic surgeons, after a period of experimental training with animals and joining participation with general surgeons in the first cases. It is suggested that gynaecologic surgeons may be able to perform laparoscopic bowel resections for endometriosis, if properly trained, although the results may not be reproducible. RECENT FINDINGS: A review of recent literature related to laparoscopic bowel resections for endometriosis showed that the learning curve and experience of the surgeon may be the most important predictive factors for the effectiveness of the procedure. Results concerning major operative complications and clinical remission were considered satisfactory in both single and multidisciplinary approaches, that is, laparoscopic bowel resections performed by gynaecologic and colorectal surgeons. Protective colostomies or ileostomies could not reduce the rate of rectovaginal fistulae in multidisciplinary experiences. SUMMARY: The single-surgeon model approach in laparoscopic excision of endometriosis that includes bowel resection may provide advantages for both the patients and healthcare system. The best model should be decided on the maximum benefit of the patient.

The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a review.

PURPOSE: endometriosis and its associated infertility have been the object of continuous research for over a century. To understand the molecular mechanisms underlying the disease, it has become necessary to determine the aspects of its etiology that are not explained by the retrograde menstruation theory. This could in turn elucidate how various clinical and surgical treatments might affect the evolution and remission of the disease. METHODS: this review is focused on the most recent clinical and laboratory findings regarding the association of HOXA10 with endometriosis and infertility. RESULT: the homebox (Hox/HOX) proteins are highly conserved transcription factors that determine segmental body identities in multiple species, including humans. Hoxa10/HOXA10 is directly involved in the embryogenesis of the uterus and embryo implantation via regulation of downstream genes. Cyclical endometrial expression of Hoxa10/HOXA10, with a peak of expression occurring during the window of implantation, is observed in the adult in response to estrogen and progesterone. Women with endometriosis do not demonstrate the expected mid-luteal rise of HOXA10 expression, which might partially explain the infertility observed in many of these patients. Recent studies also demonstrated HOXA10 expression in endometriotic foci outside the Müllerian tract. CONCLUSIONS: multiple lines of evidence suggest that the actions of the homeobox A10 (Hoxa10/HOXA10) gene could account for some aspects of endometriosis.

Postoperative imaging findings after laparoscopic surgery for deeply infiltrating endometriosis.

Deeply infiltrative endometriosis (DIE) is a common gynecologic disease affecting women of reproductive age and often causing chronic pelvic pain and infertility. Clinical treatment options and preventive actions are ineffective due to the lack of knowledge about the etiology of DIE. Surgical treatment is currently the only alternative to eradicate the disease. Diagnostic imaging plays a crucial role for surgical planning and postoperative evaluation. Transvaginal sonography (TVS) with a dedicated protocol and magnetic resonance imaging (MRI) can be used to evaluate recurrent disease. Extensive pelvic surgery may cause anatomical changes and a variable spectrum of postoperative findings. Residual disease and complications can be also evaluated and are of great importance to estimate pain relief and fertility prognosis. The most common imaging findings following radical surgery for DIE are fibrotic scars in the retrocervical space and bowel anastomosis, absence of the posterior vaginal fornix and loculated fluid in the pararectal spaces. Ovaries are the most frequent site of early recurrence. Complications include infection, hemorrhage, urinary/evacuatory voiding dysfunctions as well as bowel and ureteral stenosis. The purpose of this article is to review the surgical techniques currently used to treat endometriosis in the retrocervical space, vagina, bladder, bowel, ureters, and ovaries and to describe the most common imaging findings including normal aspects, residual disease, complications, and recurrence.

Endometrial claudin-4 and leukemia inhibitory factor are associated with assisted reproduction outcome.

BACKGROUND: Claudin-4 (CLDN4) is one of several proteins that act as molecular mediators of embryo implantation. Recently, we examined immunolabeling of leukemia inhibitory factor (LIF) in the endometrial tissue of 52 IVF patients, and found that LIF staining intensity was strongly correlated with successful pregnancy initiation. In the same set of patients, we have now examined endometrial CLDN4 expression, to see how expression intensity may vary with LIF. We examined CLDN4 in the luteal phase of the menstrual cycle, immediately preceding IVF treatment. Our aim was to compare expression of LIF and CLDN4 in the luteal phase, and document these patterns as putative biomarkers for pregnancy. METHODS: Endometrial tissue was collected from women undergoing IVF. Endometrial biopsies were obtained during the luteal phase preceding IVF, and were then used for tissue microarray (TMA) immunolabeling of CLDN4. Previously published LIF expression data were then combined with CLDN4 expression data, to determine CLDN4/LIF expression patterns. Associations between successful pregnancy after IVF and combined CLDN4/LIF expression patterns were evaluated. RESULTS: Four patterns of immunolabeling were observed in the endometrial samples: 16% showed weak CLDN4 and strong LIF (CLDN4-/LIF+); 20% showed strong CLDN4 and strong LIF (LIF+/CLDN4+); 28% showed strong CLDN4 and weak LIF (CLDN4+/LIF-); and 36% showed weak CLDN4 and weak LIF (CLDN4-/LIF-). Successful implantation after IVF was associated with CLDN4-/LIF+(p = 0.003). Patients showing this endometrial CLDN4-/LIF+ immunolabeling were also 6 times more likely to achieve pregnancy than patients with endometrial CLDN4+/LIF- immunolabeling (p = 0.007). CONCLUSION: The combined immunolabeling expression of CLDN4-/LIF+ in endometrial tissue is a potential biomarker for predicting successful pregnancy in IVF candidates.

Human choriogonadotropin prior to controlled ovarian stimulation and in vitro fertilization improves implantation, and pregnancy rates.

PURPOSE: Our purpose was to retrospectively compare controlled ovarian stimulation(COH) in IVF cycles with administration of hCG on the day of menses (D1-hCG) with women not receiving hCG at day 1 of menses (Control). METHODS: Data on maternal age, endocrine profile, amount of rFSH required, embryo characteristics, implantation and pregnancy rates were recorded for comparison between D1-hCG (n = 36) and Control (n = 64). RESULTS: Dose of rFSH required to accomplish COH was significantly lower in D1-hCG. Following ICSI, more top-quality embryos were available for transfer per patient in the D1-hCG and biochemical pregnancy rates per transfer were significantly higher in the D1-hCG. Significantly higher implantation and on-going pregnancy rates per embryo transfer were observed in D1-hCG (64%) compared to Control (41%). CONCLUSIONS: Administration of D1-hCG prior to COH reduces rFSH use and enhances oocyte developmental competence to obtain top quality embryos, and improves implantation and on-going pregnancy rates. At present it is not clear if the benefit is related to producing an embryo that more likely to implant or a more receptive uterus, or merely fortuitous and related to the relatively small power of the study.

Prognostic factors for pregnancy after intrauterine insemination.

OBJECTIVE: To evaluate prognostic factors for pregnancy after intrauterine insemination (IUI). METHODS: A retrospective study was conducted among couples who underwent IUI at Universidade de São Paulo, Brazil, between January 31, 2008, and April 30, 2016. The main outcome was a positive ß human chorionic gonadotropin (ß-hCG) test result after IUI. Univariate analyses were used to determine predictors of pregnancy. Selected numerical variables were categorized to maximize the area under the receiver operating characteristic (ROC) curve. Logistic regression was performed using the backward method. The quality of the model was evaluated using the R2 (Nagelkerke) and Hosmer-Lemeshow tests. RESULTS: Of 355 insemination cycles, 56 (15.8%) resulted in a positive ß-hCG test result. The predictors and cutoff values that maximized the area under the ROC curve were as follows: follicle-stimulating hormone (<7.7 mIU/mL; P<0.001); duration of infertility (<62 menses; P<0.001); number of follicles greater than or equal to 14 mm (>1 follicle; P<0.001); baseline spermatozoa concentration (>52.0 million/mL; P=0.007); total ejaculate (>123.7 million; P=0.003); and grade B motility (>35%; P=0.013). These factors were able to predict 50.4% of the positive test results (R2 ). CONCLUSION: Prognostic factors for pregnancy identified approximately half of all successful outcomes after IUI.