Day-5 fresh embryo transfer is associated with superior clinical outcomes in oocyte donation cycles compared with day-3 embryo transfer.

OBJECTIVE: Τo compare clinical outcomes between day-5 (D5ET) and day-3 (D3ET) fresh embryo transfer in oocyte donation cycles. STUDY DESIGN: A retrospective analysis of prospectively collected cohort data was performed enrolling all participants in an oocyte donation program performed either D5ET or D3ET regarding the period from June 2006 to June 2018. Cycles were compared by the day of embryo transfer. Primary outcomes were the clinical pregnancy rate and live birth rate. Secondary outcomes were implantation rate, biochemical pregnancy rate, early miscarriage rate, and twin pregnancy rate. Outcomes were adjusted for covariates within study groups. RESULTS: A total of 8023 cycles meeting our inclusion criteria were analyzed. D5ET consisted of 4865 cycles and D3ET of 3158 cycles. The D5ET group had a significantly higher clinical pregnancy rate (p < .001), live birth rate (p = .004), implantation rate (p < .001), and twin pregnancy rate (p = .02) than the D3ET group. Accordingly, biochemical pregnancy rate (7.4% vs. 5.1%, p < .001) and early miscarriage rate (4.1% vs. 3.2%, p = .04) were significantly higher in D3ET compared to the D5ET group. CONCLUSION: Οocyte donation cycles with fresh D5ET resulted in fewer embryos transferred, higher clinical pregnancy rates, and higher live birth rates compared to D3ET. Our findings are strongly favoring day-5 embryo transfer in oocyte donation cycles.

Single layer suturing in intracapsular myomectomy of intramural myomas is sufficient for a normal wound healing.

STUDY OBJECTIVE: To evaluate surgical outcomes of intracapsular single-layer myomectomy in terms of efficacy and safety as well as examine potential alterations based on kind of surgical approach. METHODS: A prospective observational study was performed between January 2010 and December 2018. Women in reproductive age, affected by intramural or subserous myomas (FIGO type 3-6) of 4-14 cm diameter were enrolled. Primary outcomes included initial and final uterine incision length, time to wound healing and uterine rupture in subsequent pregnancies. Furthermore, a sub-analysis was also performed regarding surgical approach, namely laparoscopical or laparoscopically-assisted myomectomy, in order to confirm whether overall observations are similar for both potential surgical approaches. RESULTS: There were finally 273 patients included in the present study. Overall mean uterine incision was initially 3.1 cm and was shortened to 2.2 cm at the end of operation, indicating a reduction of 29.1 %. Mean estimated blood loss was 154.2 mL and mean operative time was 82.1 min. No severe intraoperative and postoperative complications were presented. 121 of the studied women had pregnancy 3-36 months after myomectomy, without reporting any uterine rupture. When comparing LIM vs. LAIM, all outcomes were also favorable in the total of patients. CONCLUSION: Intracapsular myomectomy either by LIM or LAIM is a safe and attractive alternative to abdominal myomectomy in setting of premenopausal patients with myomas up to 14 cm. A single-layer continuous suturing in intracapsular myomectomies is enough for a successful wound healing.

Declining Sperm Counts or Rather Not? A Mini Review.

IMPORTANCE: Temporal global trends of sperm quality remain a matter of debate. OBJECTIVE: The aim of this study was to present a comprehensive review of studies reporting on sperm quality counts, summarize the main end points, and assess the main reasons for potential discrepancies. EVIDENCE ACQUISITION: An evidence-based review of PubMed and Scopus databases was performed regarding studies reporting on modification of sperm quality counts, independently of study character, study language, or date. RESULTS: Since the meta-analysis of Carlsen et al in 1992 (Br Med J 1992;305:609-613) that suggested an annual decline in sperm count of 1%, several reports confirmed the decline in sperm quality, whereas others disproved them, suggesting a slight increase or absence of change in sperm count. Such controversies may be attributed to geographical and time-related variability in sperm values and also to several confounding factors that influence the semen parameters. Intrinsic weaknesses of the studies include heterogeneity of subjects recruited, lack of adjustment for confounding factors, and samples that do not always represent the general population. CONCLUSIONS: No consensus exists on whether sperm counts actually decrease because studies' results are often controversial or inconclusive with methodological deficiencies. More prospective, large-scale, population based studies are needed in order to provide sound evidence of possible global trends in sperm count.

Unexplained infertility patients present the mostly impaired levels of progesterone receptors: Prospective observational study.

PROBLEM: Τo assess the endometrial expression of progesterone receptors in various subgroups of infertile women during implantation window. ΜETHODS: A prospective observational study was performed during March 2013-February 2017. Infertile women were categorized to those with tubal factor, ovarian failure, endometriosis or unexplained infertility. Endometrial biopsy was obtained on 7th-8th postovulatory day. Total progesterone receptors' PR(A + B) and type-B receptors' (PR-B) expression were compared between all categories of infertile and fruitful controls. RESULTS: There were overall 30 patients with tubal factor infertility (group 1), 30 with ovarian failure (group 2), 20 with endometriosis (group 3) and 20 with unexplained infertility (group 4). The control group consisted of 30 fertile patients. Patients with unexplained infertility presented the lowest levels of epithelial endometrial expression both regarding PR(A + B) and PR-B receptors. PgR(A + B) h-score in luminal epithelial cells was 106.4 ± 14.7 for cases with unexplained infertility vs 219.7 ± 15.8 for controls (P < .001). Similarly, PgR(A + B) h-score in glandular epithelial cells was 109.7 ± 13.9 vs 220.1 ± 17.2 (P < .001). Relative remarks were made for type-B progesterone receptors. CONCLUSION: Εndometrial expression of progesterone receptors is impaired in women with unexplained infertility. Therapeutic strategies targeting on improving progesterone receptors' expression may significantly affect final reproductive outcome.

GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial.

PURPOSE: The purpose this study is to investigate whether a double antagonist dose (0.25 mg/12 h) administered the day before hCG trigger is effective in preventing ovarian hyperstimulation syndrome (OHSS) in GnRH antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles at risk for OHSS. METHODS: This is a prospective randomized control study, conducted from November 2012 to January 2016. A total of 194 patients undergoing a IVF/ICSI GnRH antagonist cycle that were at risk of OHSS and chose to proceed with embryo transfer and avoid cycle cancellation or embryo cryopreservation were allocated into two groups. The inclusion criteria consisted of a rapid rise of oestradiol ≥ 3500 pg/ml combined with ≥ 18 follicles > 11 mm in diameter without any mature follicle > 16 mm, in any day of stimulation. Overall, 97 patients (intervention group A) received a double dose of GnRH antagonist (0.25 mg/12 h) the day before hCG while 97 patients (control group B) did not. Recombinant FSH administration was tapered to 100 IU/24 h the day of the allocation in both groups. RESULTS: Incidence of early-onset moderate/severe OHSS was significantly lower in intervention group A compared to control group B (0 vs 12.37%, P < 0.001). Clinical pregnancy rate per cycle (50.52 vs 42.27%, P = 0.249) was not significantly different between the two groups. Oestradiol (3263.471 ± 1271.53 vs 5233 ± 1425.17, P < 0.001), progesterone (0.93 ± 0.12 vs 1.29 ± 0.14, P < 0.001) and luteinizing hormone (1.42 ± 0.31 vs 1.91 ± 0.33, P < 0.001) were significantly lower in group A the day of the hCG triggering. CONCLUSION: The administration of a rescue double GnRH antagonist dose the day before hCG trigger may represent a safe alternative preventive strategy for early OHSS without affecting the reproductive outcomes. TRIAL REGISTRATION NUMBER: ISRCTN02750360.

LIF endometrial expression is impaired in women with unexplained infertility while LIF-R expression in all infertility sub-groups.

The main objective of our study was to study LIF and LIF-R endometrial expression during the implantation window in the various sub-groups of infertile women according to infertility cause. A prospective observational case-control study was performed from March 2013 to February 2016. Infertile women consisted of the patients' group (group 2) while fertile women were the control group (group 1). Infertile women were divided according to infertility cause in women with tubal factor (group 2a), poor ovarian reserve (group 2b), endometriosis (group 2c) and unexplained infertility (group 2d). Endometrial biopsy was performed on 7th-8th postovulatory menstrual day. Leukemia Inhibitory Factor (LIF) and LIF-Receptor (LIF-R) expression in epithelial and stromal cells were assessed with Immunohistochemistry (IHC). There were 20 infertile with poor ovarian reserve, 15 with tubal factor, 10 with endometriosis and 15 with unexplained infertility included in the analysis. LIF expression in patients with unexplained infertility was significantly compared with controls (P=0.006). No significant difference was observed between patients with tubal factor, poor ovarian reserve and endometriosis compared with control group (P=0.78, P=0.44 and P=0.56 respectively). Analysis of LIF-R expression in sub-categories of infertility indicated that expression was significantly decreased in all sub-groups of infertility. Our study indicated impaired LIF expression levels only in women with unexplained infertility, while LIF-R expression was impaired in all sub-groups of infertile women. Further multicenter prospective studies should be performed in order to assess the exact etiopathogenetic role of these cytokines in the molecular background of infertility.

LIF and LIF­R expression in the endometrium of fertile and infertile women: A prospective observational case­control study.

The aim of the present study was to determine the expression of leukemia inhibitory factor (LIF) and LIF receptor (LIF­R) in the endometrium of fertile and infertile women during the implantation window. A prospective study was conducted between March 2013 and March 2015 at Iakentro, Infertility Treatment Center (Thessaloniki, Greece) and the 3rd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki (Thessaloniki, Greece). The patient group consisted of women diagnosed with infertility, whereas the control group consisted of women who had delivered at least one live newborn (fertile women). An endometrial biopsy was obtained using a Pipelle on day 7 or 8 post­ovulation, and the expression of LIF and LIF­R was assessed by immunohistochemistry in epithelial and stromal cells. Primary outcomes included positive cellular percentage, staining intensity and H­score. P<0.05 was considered to indicate a statistically significant difference. Overall, 45 women were included in the present analysis (15 fertile women and 30 infertile women). Mean age was 32.8±6.0 years for the fertile group, and 37.6±3.7 for the infertile group. LIF and LIF­R expression was significantly reduced in the epithelial cells of infertile women (P=0.05 and P=0.006, respectively). However, no significant differences were detected with regards to the expression of LIF in stromal cells (P=0.95). In addition, LIF­R expression was relatively higher in the stromal cells of the fertile group; however, the difference did not reach statistical significance (P=0.10). In conclusion, endometrial expression of LIF and LIF­R is significantly reduced in the epithelial cells of infertile women. Expression patterns of LIF­R in stromal cells require further research in order to achieve definitive results.

Expression of progesterone receptors is significantly impaired in the endometrium of infertile women during the implantation window: a prospective observational study.

OBJECTIVE: To compare the expression of progesterone receptors (A + B) and type-B progesterone receptors in the epithelial and stromal cells of fertile and infertile women. METHODS: Women were divided into two groups, the group of fertile controls (group 1) and the group of infertile women (group 2) and were set on regular ultrasound imaging in order to detect ovulation. An endometrial biopsy was obtained on the seventh or eighth post-ovulatory day. Immunohistochemistry was performed to measure percentage of positive nuclei, intensity of staining and h-score for progesterone receptors (PgR) (A + B) as well as type-B progesterone receptors in epithelial and stromal cells. Secondary outcomes included endometrial tissue dating, the rate of tissues being out-of-phase and endometrial thickness. RESULTS: Endometrial issue was obtained from 15 fertile and 30 infertile women. Expression of PgR (A + B) and PgR type-B was significantly lower in the epithelial cells of infertile women. PgR (A + B) h-score was 220.0 ± 18.5 for fertile versus 147.3 ± 18.0 for infertile women (p = 0.02). PgR type-B h-score in epithelial cells was 166.8 ± 30.7 for fertile versus 90.8 ± 20.6 for infertile (p = 0.04). No significant difference was observed in stromal cells. CONCLUSIONS: Expression levels of PgR (A + B) as well as type-B receptors are significantly lower in the epithelial cells of infertile women during implantation window.

Factors implicated in the initiation of human parturition in term and preterm labor: a review.

After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.

History of endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes.

Due to the known adverse effect of endometriosis on gamete quality, it has always been difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects, this prospective comparative study studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same donor. The aim was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes, were divided in two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The implantation and pregnancy rates were significantly lower in the endometriosis group compared with the control group (23.81% versus 31.48%, P=0.019; 45.00% versus 58.33%, P=0.039, respectively). In oocyte donation cycles, a recipient's history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women. Infertility in endometriosis may be due to poor oocyte quality or embryos with decreased ability to implant due to impaired fertilization. There are no conclusive data on the impact of endometriosis on implantation. The already-known adverse effect of endometriosis on gamete quality makes it more difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects we studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same oocyte donor. The oocyte donation model was used in an attempt to understand whether the endometrium, the oocytes or both are affected by endometriosis. The aim of the present study was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes were divided into two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The pregnancy and implantation rates were significantly lower in the endometriosis group compared to the control group (45.00% versus 58.33%, P=0.039) and (23.81% versus 31.48%, P=0.019) respectively. In oocyte donation cycles, a recipient's history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women.