The effect of embryo catheter loading technique on pregnancy rate.

Embryo transfer is the most emotional part for patients during in vitro fertilization treatment. Over the last decade, the embryo transfer procedure has undergone numerous changes in the guidelines in order to increase pregnancy rates. One such procedure is the loading of the embryo into the catheter, a thin tube that helps us transfer embryo into the uterine cavity. Very few research studies looked closely at embryo-loading technique per se. Furthermore, different infertility laboratories use various techniques to load embryo. The aim of our study was to compare the two most popular embryo-loading techniques. In 249 women, we transferred embryo aspirated into the catheter with small droplets of air, and in the group of 244 patients, we filled catheter only with fluid. Our main outcome measured was the clinical pregnancy rate. Based on our results, we did not find that embryo-loading technique affected patient's chances of achieving pregnancy.

Cryopreservation Does Not Affect the Clinical Pregnancy Rate of Blastocysts Derived from Vitrified Oocytes.

Vitrified, or "frozen", donor eggs can either be fertilized and cultured for fresh transfer (group 1), or fertilized and cryopreserved for transfer in a "frozen embryo transfer" cycle (group 2). This study compared the pregnancy rates between the two groups. Frozen donor egg cycles (N = 1213) were analyzed at the World Egg Bank. The outcome studied was clinical pregnancy rate. Cycles included only single embryo transfers (ET) without preimplantation genetic testing (PGT). A total of 600 cycles met the inclusion criteria. Group 1 included 409 cycles and group 2 had 191 cycles. There was no statistical significance in clinical pregnancy rate between the two groups (38.63% vs 32.46%, p = 0.14). Mean embryo age was higher in group 2 (5.1 vs. 5.4 days, p < 0.01). The compounding effect of vitrification when applied to two distinct stages (oocyte and embryo), has not been studied. When comparing the two groups, we found no difference in pregnancy rate. However, there was a trend towards fewer pregnancies in group 2. A larger study should be done to determine the validity of this result (Ramadan et al. in Fertil Steril, 2020).

Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF.

STUDY QUESTION: Are perinatal outcomes improved in singleton pregnancies resulting from fresh embryo transfers performed following unstimulated/natural cycle IVF (NCIVF) compared with stimulated IVF? SUMMARY ANSWER: Infants conceived by unstimulated/NCIVF have a lower risk of being low birthweight than infants conceived by stimulated IVF; however, this risk did not remain significant after adjusting for gestation age. WHAT IS ALREADY KNOWN: Previous studies have shown that infants born after modified NCIVF have a higher average birthweight and are less likely to be low birthweight than those infants conceived with conventional stimulated IVF. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of singleton live births in non-smoking women undergoing fresh IVF-embryo transfer cycles from 2007 to 2013 in a single IVF center. The women were stratified by stimulated (n = 174) or unstimulated (n = 190) IVF exposure status. Unstimulated/NCIVF is defined as IVF without the use of exogenous gonadotrophins, and only includes the use of HCG to time oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS: Demographic data including maternal age, BMI, infertility diagnosis and IVF cycle characteristics were collected. The perinatal outcomes used for comparison between the two study groups were length of gestation, birthweight, preterm delivery, very preterm delivery, low birthweight, small for gestational age and large for gestational age. MAIN RESULTS AND ROLE OF CHANCE: Although women in the NCIVF group were older than those in the stimulated group (35.0 versus 34.2 years, P < 0.05), parity and history of prior ART cycles were comparable between the groups. The mean birthweight was significantly higher in the NCIVF group by 163 g than in the stimulated group (3436 ± 420 g versus 3273 ± 574 g, P < 0.05). Consistent with this finding, there were also less low birthweight (<2500 g) infants in the NCIVF group versus stimulated group (1 versus 8.6%, P < 0.005). The reduction in risk for low birthweight in the NCIVF group remained significant after adjustment for maternal age, infertility diagnosis, ICSI, number of embryos transferred and blastocyst transfer (odds ratio (OR) 0.07; 95% CI 0.014-0.35). As NCIVF group had less preterm infants, additional adjustment for gestational age was performed and this showed a tendency towards lower risk of low birthweight in NCIVF (OR 0.11; 95% CI 0.01-1.0). While gestational age at delivery was comparable between the groups, both preterm births (<37 weeks gestation) (31 versus 42%, P < 0.05) and very preterm births (<32 weeks gestation) (0.52 versus 6.3%, P < 0.005) were significantly reduced in the NCIVF group. However, after adjustment for potential confounders, the reduction in risk of preterm and very preterm delivery associated with the NCIVF group was no longer significant (OR 1.1; 95% CI 0.48-2.5). LIMITATIONS, REASONS FOR CAUTION: Limitations of this study are the retrospective nature of the data collection and the lack of information about parental characteristics associated with birthweight. WIDER IMPLICATIONS OF THE FINDINGS: The improved perinatal outcomes following successful unstimulated/NCIVF suggest that this treatment should be considered as a viable option for infertile couples. NCIVF could reduce potential adverse perinatal outcomes such as low birthweight related to fresh embryo transfers performed following ovarian stimulation. The etiology of the improved perinatal outcomes following NCIVF needs to be explored further to determine if the improvement is derived from endometrial factors versus follicular/oocyte factors. STUDY FUNDING/COMPETING INTERESTS: The study was supported by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD K12HD047018 (W.M.), NICHD K12HD001271 (L.A.K.). The authors have no competing interests.

Utilization and success rates of unstimulated in vitro fertilization in the United States: an analysis of the Society for Assisted Reproductive Technology database.

OBJECTIVE: To examine the utilization and outcomes of natural cycle (unstimulated) IVF as reported to the Society of Assisted Reproductive Technology (SART) in 2006 and 2007. DESIGN: Retrospective analysis. SETTING: Dataset analysis from the SART Clinical Outcome Reporting System national database. PATIENT(S): All patients undergoing IVF as reported to SART in 2006 and 2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Utilization of unstimulated IVF; description of patient demographics; and comparison of implantation and pregnancy rates between unstimulated and stimulated IVF cycles. RESULT(S): During 2006 and 2007 a total of 795 unstimulated IVF cycles were initiated. Success rates were age dependent, with patients <35 years of age demonstrating clinical pregnancy rates per cycle start, retrieval, and transfer of 19.2%, 26.8%, and 35.9%, respectively. Implantation rates were statistically higher for unstimulated compared with stimulated IVF in patients who were 35 to 42 years old. CONCLUSION(S): Unstimulated IVF represents <1% of the total IVF cycles initiated in the United States. The pregnancy and live birth rates per initiated cycle were 19.2% and 15.2%, respectively, in patients <35 years old. The implantation rates in unstimulated IVF cycles compared favorably to stimulated IVF. Natural cycle IVF may be considered in a wide range of patients as an alternative therapy for the infertile couple.

Placental growth factor is a potent vasodilator of rat and human resistance arteries.

The objectives of this study were to determine whether placental growth factor (PlGF) exerts a vasodilatory effect on rat uterine vessels (arcuate arteries and veins) and to examine regional differences in reactivity by comparing these responses to those of comparably sized mesenteric vessels. We also sought to examine and compare its effects on human uterine and subcutaneous vessels. All vessels were studied in vitro, under pressurized (rat) or isometric wire-mounted (human) conditions, and exposed to a range of PlGF concentrations. Inhibitors of nitric oxide and prostaglandin synthesis were included in an effort to understand the causal mechanism(s). In rat uterine arteries, the effects of receptor inhibition and activation using selective ligands for VEGFR-1 (PlGF) vs. VEGFR-2 (VEGF-E) were determined, and real-time RT-PCR was performed to evaluate the effect of pregnancy on relative abundance of VEGFR-1 and VEGFR-2 message in the vascular wall. PlGF was a potent vasodilator of all vessels studied, with greatest sensitivity observed in rat uterine arteries. Pregnancy significantly augmented dilator sensitivity to PlGF, and this effect was associated with selective upregulation of VEGFR-1 message in the pregnant state. The contribution of nitric oxide was appreciable in rat and human uterine arteries, with lesser effects in rat uterine veins and mesenteric arteries, and with no observable effect in human subcutaneous vessels. Based on these results, we conclude that PlGF is a potent vasodilator of several vessel types in both humans and rats. Its potency and mechanism vary with physiological state and vessel location and are mediated solely by the VEGFR-1 receptor subtype. Gestational changes in the uterine circulation suggest that this factor may play a role in modulating uterine vascular remodeling and blood flow during the pregnant state.

Effects of h1-calponin ablation on the contractile properties of bladder versus vascular smooth muscle in mice lacking SM-B myosin.

The functional significance of smooth muscle-specific h1-calponin up-regulation in the smooth muscle contractility of SM-B null mice was studied by generating double knockout mice lacking both h1-calponin and SM-B myosin. The double knockout mice appear healthy, reproduce well and do not show any smooth muscle pathology. Loss of h1-calponin in the SM-B null mice bladder resulted in increased maximal shortening velocity (V(max)) and steady-state force generation. The force dilatation pressure, which was decreased in the SM-B null mesenteric vessels, was restored to wild-type levels in the double knockout vessels. In contrast, the half-time to maximal constriction was significantly increased in the double knockout vessels similar to that of SM-B null mice and indicating decreased shortening velocity in the double knockout vessels. Biochemical analyses showed that there is a significant reduction in smooth muscle alpha-actin levels, whereas h-caldesmon levels are increased in the double knockout bladder and mesenteric vessels, suggesting that these changes may also partly contribute to the altered contractile function. Taken together, our studies suggest that up-regulation of h1-calponin in the SM-B null mice may be necessary to maintain a reduced level of cross-bridge cycling over time in the absence of SM-B myosin and play an important role in regulating the smooth muscle contraction.

Mechanism of VEGF-induced uterine venous hyperpermeability.

BACKGROUND: Transfer of molecular signals from veins to adjacent arteries is an established mechanism of vascular communication in the uterine circulation, which ultimately depends on venous permeability. This study tests the hypotheses that: (1) uterine veins are permeable to intravenous solutes, using a 3-kDa dextran tracer and (2) this permeability is enhanced in response to vascular endothelial growth factor (VEGF). Additionally, the involvement of nitric oxide (NO), calcium, and the phospholipase C-protein kinase C (PLC-PKC) cascade in VEGF-enhanced permeability were investigated, and the impact of pregnancy-induced uterine vascular remodeling on permeability was evaluated. METHODS: Studies utilized fluorimetry to quantitate solute flux in isolated segments of rat uterine vein as a function of endothelial surface area and time under basal and VEGF-stimulated conditions. VEGF signaling was probed using NO synthase inhibition (L-NNA), calcium channel blockade (lanthanum chloride) and withdrawal (calcium-free solution), and inhibitors of the PLC-PKC cascade (U-73122 and chelerythrine chloride, respectively). Gestational effects were assessed using vessels from late pregnant (day 20) rats. RESULTS: Basal flux (control) in nonpregnant animals was 26 +/- 2.5 molecules/microm2/min x 1,000 and was increased significantly by VEGF in a concentration-dependent manner (1 nM approximately 3.3-fold, 10 nM approximately 4.6-fold). Inhibition of PLC, PKC, and calcium signaling, but not NO, attenuated the response to VEGF. Gestation significantly increased flux (78 +/- 9.3 molecules/microm2/min x 1,000), and maintained responsiveness to VEGF. CONCLUSIONS: These results demonstrate uterine venous permeability to intermediate-sized solutes through a VEGF-sensitive pathway involving calcium and PLC-PKC, but not NO, and further substantiate a role for veno-arterial communication in uterine blood flow regulation during pregnancy.

Structural remodeling of rat uterine veins in pregnancy.

OBJECTIVE: This study characterized the cellular remodeling that contributes to uterine venous growth during gestation and evaluated the effect of pregnancy on the mechanical properties of the uterine vein. STUDY DESIGN: Diameter and distensibility were calculated in pressurized uterine veins from virgin and pregnant (19-20 days of gestation) rats; the rates of cellular division (endothelial, vascular smooth muscle) were quantified with an intraperitoneal bromodeoxyuridine injection and immunohistochemistry. Elastin content, adrenergic nerve density, and wall thickness were determined in fixed uterine veins and quantified with an imaging program. RESULTS: There was a statistically significant increase in the diameter and mitotic indices (endothelial, vascular smooth muscle) in uterine veins from late pregnant versus nonpregnant animals. Adrenergic nerve density was diminished significantly during gestation. Venous distensibility increased during pregnancy, with an associated reduction in elastin content. CONCLUSION: Pregnancy results in coordinated and multifaceted structural remodeling of uterine veins with subsequent changes in caliber, mechanical properties, rates of cellular division, adrenergic innervation, and matrix composition.

Venoarterial communication as a mechanism for localized signaling in the rat uterine circulation.

OBJECTIVE: Venoarterial communication describes the phenomenon whereby molecular signals in a vein directly influence an adjacent artery. The objective of this study was to investigate, in vitro, the existence of such a pathway in the uterine circulation of the rat. STUDY DESIGN: Paired uterine vessels from late pregnant and virgin rats were pressurized and studied in a dual-perfusion vasograph. Veins were perfused with phenylephrine and endothelin-1, alone or in combination, and the vasoactive responses of both vessels were recorded. RESULTS: Venous perfusion of phenylephrine resulted in concentration-dependent arterial, but not venous, constriction. Conversely, veins, but not arteries, demonstrated concentration-dependent constriction to intravenous endothelin-1. Superfusion of endothelin-1 constricted both vessels. Coperfusion of endothelin-1 and phenylephrine constricted the veins and attenuated the previously observed arterial response to intravenous phenylephrine. CONCLUSION: The results of this study support the existence of venoarterial communication within the uterine circulation through an endothelin-1-sensitive pathway.