Women Undergoing Invitro Fertilization Research Articles

Inverse association of prepregnancy systolic blood pressure and live birth rate in normotensive women undergoing in vitro fertilization/intracytoplasmic sperm injection

To explore whether maternal baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) affect pregnancy outcomes particularly in normotensive women (SBP, 90-139 mm Hg; DBP, 60-89 mm Hg) and hypertensive women undergoing invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Retrospective cohort study. Maximum care hospital for reproductive medicine. This study included 73,462 patients who underwent IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya between January 1, 2016, and November 30, 2020, selected on the basis of pre-established criteria. Analysis was limited to the first transfer cycle of the first stimulation cycle. Baseline SBP and DBP. The primary outcome focused on the live birth rate (LBR), with the secondary outcomes including clinical pregnancy rate, ectopic pregnancy rate, first-trimester miscarriage rate, second- or third-trimester fetal loss, and delivery/neonatal/maternal outcomes. Analytic methods included Poisson regression, linear regression, linear mixed-effect model, and restricted cubic spline analysis as appropriate. For normotensive women, a 10-mm Hg increase in SBP was associated with an adjusted relative risk of 0.988 (95% confidence interval, 0.981-0.995) for live birth likelihood. However, DBP was not significantly associated with LBR after adjustments. The secondary outcomes indicated that increases in SBP and DBP were associated with higher risks of first-trimester miscarriage, gestational diabetes mellitus, and gestational hypertension in the normotensive subset. Sensitivity analyses confirmed these associations between SBP/DBP and LBR, consistent with the main findings even under stricter guidelines and after adjusting for multiple confounders. Subgroup analyses showed variation in the impact of blood pressure on LBR across different demographics and conditions. Consistent with earlier studies on blood pressure and birth outcomes, we found a 10-mm Hg increase in SBP was associated with a 5.4% (adjusted relative risk per 10 mm Hg, 0.946; 95% confidence interval, 0.907-0.986) reduction in LBR in the hypertensive subgroup. Systolic blood pressure impacted LBR outcomes in normotensive women who underwent IVF/ICSI, which suggests the need for reconsidering blood pressure management guidelines for reproductive-age women, focusing on reproductive health in addition to cardiovascular risk.

NOTCH1- and CD117-positive stem cells in human endometrium and their implications for successful implantation

To investigate the quantity of 2 stem cell types in the endometrial stroma of women undergoing invitro fertilization and their association with steroid hormone signaling and implantation success after embryo transfer. Prospective cohort study. Private hospital. A total of 109 patients undergoing invitro fertilization. Not applicable. Immunohistochemistry staining of endometrial biopsies taken during the midluteal phase using antibodies against NOTCH1 and CD117 was performed. The percentage of endometrial stromal cells positive for these markers was determined. The link of these stem cell percentages with the serum progesterone and estradiol levels and the endometrial expression of their respective receptors were assessed. After embryo transfer, the quantity of stained cells for each marker was also compared according to implantation outcome. The percentage of NOTCH1+ stromal cells ranged from 0.003%-2.112% (median, 0.062%) and was significantly higher than that of CD117+ cells, which ranged from 0.000%-0.210% (median, 0.020%) (Z = -7.035). The percentage of NOTCH1+ stem cells showed no difference between the studied serum hormone level groups and no relationship with the expression of their receptors in the endometrium. In contrast, the number of CD117+ cells significantly differed between patients with high and low levels of serum progesterone (cutoff, 14.9 ng/mL) and estradiol (cutoff, 135.6 pg/mL). Furthermore, the quantity of CD117+ stem cells was positively correlated with the progesterone receptor (R = 0.277) and estradiol receptor (R= 0.318) expression levels in the endometrium. Although the quantity of NOTCH1+ cells did not differ between the 2 implantation groups, the median percentage of CD117+ cells was significantly higher in patients with successful implantation than in those with unsuccessful implantation (0.03% vs. 0.01%, respectively). The cutoff value for the percentage of CD117+ cells predicting successful implantation was 0.018% (area under the curve, 0.66; 95% confidence interval, 0.56-0.77; sensitivity, 63.1%; specificity, 61.4%). This study indicates that the quantity of certain stem cell types (CD117+), but not others (NOTCH1+), in the functional endometrium is associated with implantation success and sex hormone signaling during the midluteal phase. These findings highlight the role of CD117+ cells in preparing the endometrium for embryo implantation, and their quantity may be an indirect indicator of endometrial receptivity.

Characterizing the follicular fluid metabolome: quantifying the correlation across follicles and differences with the serum metabolome

To compare the variability in metabolomes between the serum and follicular fluid, as well as across 3 dominant follicles. Prospective cohort study. An academic fertility clinic in the northeastern United States, 2005-2015. One hundred thirty-five women undergoing invitro fertilization treatment who provided a serum sample during ovarian stimulation and up to 3 follicular fluid samples during oocyte retrieval. None. Samples were analyzed using liquid chromatography with high-resolution mass spectrometry and 2 chromatography columns (C18 hydrophobic negative and hydrophilic interaction chromatography [HILIC] positive). We calculated overall, feature-specific, and subject-specific correlation coefficients to describe how strongly the intensity of overlapping metabolic features were associated between the serum and follicular fluid and between the 1st-2nd, 1st-3rd, and 2nd-3rd follicles. Feature-specific correlations were adjusted for age, body mass index, infertility diagnosis, ovarian stimulation protocol, and year. From the C18-negative column and the high-resolution mass spectrometry, 7,830 serum features and 10,790 follicular fluid features were detected in ≥20% of samples. After screening retention times and checking for 1:1 matching, 1,928 features overlapped between the 2 metabolomes. From the HILIC-positive column and the high-resolution mass spectrometry, after applying the same exclusion criteria, there were 9,074 serum features, 5,542 follicular fluid features, and 1,149 features that overlapped. When comparing the feature intensity of overlapping metabolites in the serum and the follicular fluid, the overall (C18, 0.45; HILIC, 0.63), median feature-specific (C18, 0.35; HILIC, 0.37), and median subject-specific (C18, 0.42; HILIC, 0.59) correlations were low to moderate. In contrast, among the overlapping features across all 3 follicles, the overall (C18, all 0.99; HILIC, all 0.99), median feature-specific (C18, 0.74-0.81; HILIC, 0.79-0.85), and median subject-specific (C18, 0.88-0.89; HILIC, 0.90-0.91) correlations between follicular fluid metabolomics features within a woman were high. We observed minimal overlap and weak-to-moderate correlation between metabolomic features in the serum and follicular fluid but a large overlap and strong correlation between metabolomic features across follicles within a woman. The follicular fluid appears to represent a novel matrix, distinct from serum, which may be a rich source of biologic predictors of female fertility and reproductive outcomes.

Shorter telomere length of white blood cells is associated with higher rates of aneuploidy among infertile women undergoing in vitro fertilization

To evaluate whether the telomere length of white blood cells (WBC) and cumulus cells (CC) in an infertile population is associated with ovarian and embryonic performance. Prospective cohort study. Academic-affiliated private practice. A total of 175 infertile women undergoing invitro fertilization (IVF) at a single center between July 2017 and December2018. On the day of oocyte retrieval, genomic DNA was isolated from WBC and CC samples. Telomere length assessment was performed for both tissue types using quantitative real-time polymerase chain reaction. Telomere lengths were normalized using an AluYa5 sequence as an endogenous control, and linear regressions were applied. This study assessed the relationship between relative telomere length of WBC and CC samples and measures of ovarian and embryonic performance. Specifically, patient age, antimüllerian hormone (AMH) level, peak estradiol (E2) level, number of oocytes retrieved, number of mature (MII) oocytes retrieved, blastulation rate, and aneuploidy rate were assessed. There was a statistically significant relationship between WBC relative telomere length and patient age as well as rates of embryonic aneuploidy, with shorter WBC relative telomere length associated with increasing patient age (P<.01) and higher rates of aneuploidy (P=.01). No statistically significant relationships were observed between WBC relative telomere length and the other outcome measures. No significant associations were noted between CC relative telomere length and any outcomes assessed in this study. The relationship between WBC relative telomere length and aneuploidy warrants further investigation, particularly because significant overlap exists between increasing maternal age and rates of embryonic aneuploidy.

Interpretation of noninvasive prenatal testing results following in vitro fertilization and preimplantation genetic testing for aneuploidy

The positive predictive value of noninvasive prenatal testing is approximately 69% in the general population. However, positive predictive value is dependent on the prevalence of the disease in the population being tested. Patients who undergo invitro fertilization with preimplantation genetic testing for aneuploidy and transfer a euploid embryo are presumably a lower risk population than the general population. In this study, we explored the positive predictive value of noninvasive prenatal testing in women undergoing invitro fertilization with preimplantation genetic testing for aneuploidy and subsequent transfer of a euploid embryo. This study was a retrospective cohort study. All patients who underwent invitro fertilization with preimplantation genetic testing for aneuploidy followed by transfer of a single euploid embryo between 2014 and 2019 at a university-affiliated fertility center were contacted. Noninvasive prenatal testing results were reviewed and those with positive noninvasive prenatal testing were identified. Results of any subsequent prenatal or postnatal diagnostic testing were used to classify each positive noninvasive prenatal testing as a true positive or a false positive. The prevalence and positive predictive value of positive noninvasive prenatal testing was calculated. A total of 1139 patients that underwent noninvasive prenatal testing after transfer of a euploid embryo were identified, 8 of which had positive noninvasive prenatal testing screens. Although 6 of these patients had subsequent definitive prenatal diagnostic testing that revealed a euploid karyotype concordant with their preimplantation genetic testing for aneuploidy results, 1 patient opted out of diagnostic testing and later delivered a normal baby. Of note, 1 patient who had noninvasive prenatal testing positive for Turner syndrome underwent amniocentesis, which confirmed Turner mosaicism (45,X karyotype in 80% of cells). Therefore, the positive predictive value of noninvasive prenatal testing in this patient cohort was 12.5%. Clinicians and patients should recognize that patients undergoing transfer of a euploid embryo are at a relatively lower risk for fetal aneuploidy than the general population, and the positive predictive value of noninvasive prenatal testing is lower in this setting.

Female infertility is associated with an altered expression of the neurokinin B/neurokinin B receptor and kisspeptin/kisspeptin receptor systems in ovarian granulosa and cumulus cells

To analyze and compare the expression profile of TAC3, TACR3, KISS1, and KISS1R in mural granulosa and cumulus cells from healthy oocyte donors and patients with different infertility etiologies, including advanced maternal age, endometriosis, and low ovarian response. Genetic association study. Private fertility clinic and public research laboratory. Healthy oocyte donors and infertile women undergoing invitro fertilization (IVF) treatment. IVF. Gene expression levels of KISS1, KISS1R, TAC3, and TACR3 in human mural granulosa and cumulus cells. Infertile women showed statistically significantly altered expression levels of KISS1 (-2.57 ± 2.30 vs. -1.37 ± 2.11), TAC3 (-1.21 ± 1.40 vs. -1.49 ± 1.98), and TACR3 (-0.77 ± 1.36 vs. -0.03 ± 0.56) when compared with healthy oocyte donors. Advanced maternal age patients, endometriosis patients, and low responders showed specific and altered expression profiles in comparison with oocyte donors. Abnormal expression levels of KISS1/KISS1R and TAC3/TACR3 systems in granulosa cells might be involved in the decreased fertility associated to advanced maternal age, endometriosis, and low ovarian response.

Effect of pretreatment oral contraceptives on fresh and cumulative live birth in vitro fertilization outcomes in ovulatory women

To evaluate the impact of oral contraceptives (OC) on live birth rate (LBR) following a fresh embryo transfer and cumulative live birth rate (cLBR) in normal ovulatory women undergoing invitro fertilization (IVF). Retrospective cohort study. Reproductive center. A total of 3,110 normo-ovulatory women aged 20-40 years undergoing IVF either using or not using OC pretreatment in their first autologous cycle. Patients initiated gonadotropins for their IVF cycle either after a spontaneous menses or following OC pretreatment, which was at the discretion of the provider or according to patients preference. The primary outcomes were LBR after fresh transfer (fLBR) and cLBR. fLBR was significantly lower in women using OC compared to those not (42.6% vs. 52.8%). Although LBR after frozen embryo transfer cycles were similar (42.7% vs. 41.1%), cLBR was significantly lower in women using OC (62.8% vs. 67.6%). Multivariate logistic and COX regression analysis adjusting for baseline characteristics demonstrated that IVF cycle synchronization with OC was significantly associated with a lower fLBR (adjusted odds ratio 0.73, 95% confidence interval 0.62-0.86) and cLBR (adjusted hazard ratio 0.89, 95% confidence interval 0.80-0.98). Pretreatment OC use is associated with a reduction in fLBR and cLBR.

The Origin of Follicular Bile Acids in the Human Ovary

Bile acids (BAs) are present in ovarian follicular fluid (FF) and are linked to embryo development. However, information on the source of ovarian BA is scarce. Therefore, we aimed to explore local ovarian synthesis and BA transport from blood into FF. BA levels were determined in matching FF and serum from women undergoing invitro fertilization. Invitro BA production by human mural granulosa cells (MGCs) and cumulus granulosa cells (CGCs) was measured by mass spectrometry. Gene and protein expression were quantified in MGC and CGC and in human ovarian tissue by quantitative PCR and Western blot/immunohistochemistry, respectively. BA levels in blood and FF were significantly correlated (rs=0.186, P=0.027) but were almost twofold higher in FF (P<0.001). Primary BA levels were increased in FF, indicating that, in addition to passive diffusion, other sources of ovarian BA might exist. The key BA synthesis enzyme cytochrome P450 A1 was absent in MGC and CGC; BA production invitro was undetectable. Therefore, local ovarian BA production is unlikely. However, common BA importers (Na+/taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter) and an exporter (ATP-binding cassette subfamily C member 3) were identified in GC, theca cells, and oocyte. In summary, these results suggest that passive and active transport of BAs from blood into FF constitute sources of FF BA.

Long-term cryostorage of semen in a human sperm bank does not affect clinical outcomes

To evaluate the affect of the duration of donor sperm storage on pregnancy success among women undergoing assisted reproduction. Retrospective cross-sectional study. Sperm bank. A total of 119,558 specimens retrieved using a clinical information database of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from 2001 to2016. Analysis of semen samples and clinical outcomes after semen use. Clinical information included semen parameters before and after freezing, clinical pregnancy, abortion and live birth rates after semen use. The sperm's frozen-thaw survival rate decreased from 85.72% to 73.98% after 15years of cryopreservation (P<.01). The clinical pregnancy rate of women undergoing artificial insemination with donor sperm was 23.09%, 22.36% and 22.32%, the clinical abortion rate was 10.06%, 10.02% and 12.00% and the live birth rate was 82.17%, 80.21% and 80.00% in the groups with 0.5-5, 6-10 and 11-15 storage years, respectively. The clinical pregnancy rate of women undergoing invitro fertilization was 64.29%, 64.94% and 53.48%, the clinical abortion rate was 12.26%, 11.38% and 17.39% and the live birth rate was 81.63%, 79.11% and 73.91%, in the groups with 0.5-5, 6-10 and 11-15years, respectively. The long-term cryostorage of semen in a human sperm bank does not affect clinical outcomes. However, cryopreservation longer than 5years negatively influenced the quality of frozen-thawed donor sperm samples.

Quality of life and pregnancy outcomes among women undergoing in vitro fertilization treatment: A longitudinal cohort study

This study assessed the quality of life (QoL) and pregnancy outcomes among infertile women undergoing invitro fertilization (IVF) treatment to investigate the association between QoL and IVF pregnancy outcomes. This study included 686 women with 1205 embryo transfers (ETs). QoL was measured using the fertility quality of life (FertiQoL) tool before ET. FertiQoL comprises two modules: a Core module (including mind/body, emotional, relational, and social domains) and a Treatment module (covering treatment environment and tolerability domains). The FertiQol total and subscale scores were computed and scored in the range of 0-100 (higher scores indicate better QoL). Multivariate generalized estimating equation analyses were carried out to assess the association between QoL and IVF pregnancy outcomes, with adjustment for time-varying factors across multiple ETs for a given person. The lowest score in the core module was for the emotional domain (62.0), and that in the Treatment module was for the tolerability domain (59.4). QoL scores were significantly and positively associated with pregnancy outcomes (i.e., ongoing pregnancy, live birth); with a one unit increase in the emotional domain score, the probabilities of ongoing pregnancy and live birth significantly increased by 2.4% and 2.6%, respectively (p<0.05). This study evaluated the prospective association between QoL and IVF pregnancy outcomes among infertile women. The results highlight the importance of developing clinical strategies to improve QoL among infertile women undergoing IVF treatment, which may further improve the pregnancy rates of this population.

Body mass index in relation to extracellular vesicle–linked microRNAs in human follicular fluid

To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EV-linked miRNAs) in human follicular fluid. Cross-sectional study. Tertiary-care university-affiliated center. One hundred thirty-three women undergoing invitro fertilization (IVF) were recruited from January 2014 to August2016. None. EV-linked miRNAs were isolated from follicular fluid and their expression profiles were measured with the use of the Taqman Open Array Human miRNA panel. EV-linked miRNAs were globally normalized and inverse-normal transformed. Associations between body mass index (BMI) and EV-linked miRNA outcomes were analyzed by means of multivariate linear regression and principal component analysis. Eighteen EV-linked miRNAs were associated with an increase in BMI after adjusting for age, ethnicity, smoking status, and batch effects. Hsa-miR-328 remained significant after false discovery rate adjustments. Principal component analyses identified the first principal component to account for 40% of the variation in our EV-linked miRNA dataset, and adjusted linear regression found that the first principal component was significantly associated with BMI after multiple testing adjustments. Using Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we predicted gene targets of EV-linked miRNA in silico and identified PI3K-Akt signaling, ECM-receptor interaction, focal adhesion, FoxO signaling, and oocyte meiosis pathways. These results show that a 1-unit increase in BMI is associated with altered follicular fluid expression of EV-linked miRNAs that may influence follicular and oocyte developmental pathways. Our findings provide potential insight into a mechanistic explanation for the reduced fertility rates associated with increased BMI.

Follicular fluid concentrations of phthalate metabolites are associated with altered intrafollicular reproductive hormones in women undergoing in vitro fertilization

To explore whether follicular fluid (FF) concentrations of phthalate metabolites are associated with levels of intrafollicular reproductive hormones in women undergoing invitro fertilization. Cross-sectional study. University-affiliated reproductive medicine center. A total of 194 women each contributed one FF sample at oocyte retrieval. FF aspirates from individual follicles (≥18mm in diameter) were collected. We measured eight phthalate metabolites and four ovarian hormones in the FF samples. Per-follicle E2, P, total T, and antimüllerian hormone (AMH) concentrations. Most phthalate metabolites were highly detected in FF samples. We observed a dose-response relationship between increasing monomethyl phthalate (MMP) tertiles and lower E2, P, and T levels. Women in the third tertile of MMP had decreases of 34.23%, 9.44ng/L, and 23.28% in E2, P, and T, respectively, compared with women in the first tertile. Tertiles of monoethyl phthalate and the percentage of di(2-ethylhexyl) phthalate) metabolites excreted as mono(2-ethylhexyl) phthalate were inversely associated with P. We also identified a negative relationship between monobenzyl phthalate tertiles and AMH. In addition, positive correlations between some of the phthalate metabolites and ovarian hormones were detected. FF concentrations of certain phthalate metabolites were associated with altered levels of intrafollicular reproductive hormones, which raises concern over a potential deleterious effect of environmental phthalate exposure on the endocrine capacity and viability of theca and granulosa cells.

External validation of a prediction model to select the best day-three embryo for transfer in in vitro fertilization or intracytoplasmatic sperm injection procedures

To evaluate the multivariate embryo selection model by van Loendersloot etal. (2014) (VL) in a different geographical context. This is a retrospective external validation study of a 5-year cohort of women undergoing invitro fertilization or intracytoplasmatic sperm injection. Two outpatient fertility clinics. A total of 1,197 women who underwent 1,610 fresh invitro fertilization or intracytoplasmatic sperm injection cycles with single embryo transfer were included. None. The area under the receiver operating characteristics curve for diagnostic efficacy was used to assess the discriminative value of the model. Calibration for testing the validity of the VL model was performed using the Hosmer-Lemeshow goodness-of-fit test and a calibration plot. Three hundred thirty-three patients (21%) achieved a viable pregnancy of at least 11weeks. The area under the receiver operating characteristics curve using the VL model was 0.68. No significant difference between the predicted implantation rate and the observed implantation rates was showed using the Hosmer-Lemeshow (X2= 6.70). The calibration plot showed an intercept of the regression line of 0.34 and the estimated slope was 0.72. The investigated VL model was able to distinguish between higher and lower implantation potential of embryos in our clinical setting.

Efficacy of Cabergoline in the Prevention of Ovarian Hyperstimulation Syndrome: A Randomized, Double-blind and Placebo-controlled Trial

ABSTRACTIntroductionOvarian hyperstimulation syndrome (OHSS) is an iatrogenic complication that arises due to assisted reproductive technologies (ARTs) during infertility treatment. Recently, the use of selective dopamine receptor agonists on D2 receptors (e.g., cabergoline) has been suggested in the prevention of OHSS. The aim of this study was to evaluate the effect of cabergoline in the prevention of OHSS in high-risk patients undergoing ART.Materials and methodsThis was a randomized, double-blind, parallel group (cabergoline group and placebo) study. A total of 110 women undergoingin vitrofertilization (IVF)–intracytoplasmic sperm injection procedure using a long agonist protocol with high risk for OHSS were recruited for the study on the day of final trigger. All the patients were followed up every 48 hours for 10 days from the day of the final trigger and clinically assessed with ultrasound and blood tests. The size of ovaries and fluid collection in the pouch of Douglas (POD) was measured with ultrasound. A sample size of 92 subjects was calculated for the study to be powered at 80%. Assuming a drop-out rate of 10%, 110 subjects were enrolled for the study.ResultsThere was no significant difference observed in the size of right and left ovary, POD fluid volume, total leukocyte count (TLC), and serum estradiol level (E2 level) between both the groups from day 0 to day 8, except packed cell volume. No significant difference was observed in the incidence rate of moderate OHSS between both groups (p = 0.728). The differences in clinical pregnancy rate, implantation rate, and live birth rate were also insignificant.ConclusionCabergoline does not reduce the incidence of moderate OHSS when compared with placebo. Large, well-designed studies are needed to evaluate the effectiveness of cabergoline when used for the prevention of OHSS.How to cite this articleSingh S, Singh S, Raman AK, Ramakrishnan S, Ashraf CM. Efficacy of Cabergoline in the Prevention of Ovarian Hyperstimulation Syndrome: A Randomized, Double-blind and Placebo-controlled Trial. Int J Infertil Fetal Med 2017;8(2):54-60

Humid versus dry incubator: a prospective, randomized, controlled trial

To evaluate the efficacy of a dry versus humidified incubator on human embryo development exvivo. Prospective, double-blind, randomized, controlled trial. Private fertility centers. A total of 297 women undergoing invitro fertilization randomized into two groups. From days 0 to day 5 or 6 of culture, intervention group embryos exposed to dry culture and control group embryos exposed to humidified culture. Subsequent ongoing pregnancy rate. After transfer of embryos, there were statistically significantly lower rates of clinical and ongoing pregnancy in the dry culture arm than in the humidified culture arm (odds ratio [OR] 0.57; 95% confidence interval [CI], 0.36-0.91; versus OR 0.54; 95% CI, 0.34-0.85). On day 3 of culture, embryo quality and compaction were lower in the dry culture group (OR 0.38; 95% CI, 0.32-0.45) than in the group exposed to humidified culture (OR 0.23; 95% CI, 0.19-0.27). On day 5 of culture, embryos in dry culture had a lower rate of blastocyst formation (OR 0.39; 95% CI, 0.33-0.46), quality (OR 0.34; 95% CI, 0.29-0.40), and cryopreservation (OR 0.41; 95% CI, 0.35-0.48). In this study, human embryos cultivated exvivo in a dry incubator had statistically significantly decreased implantation and clinical and ongoing pregnancy rates. Our findings indicate the need for larger multicenter, randomized, controlled trials. NCT01695096.

Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns

To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH). Register-based cohort study. Not applicable. Women undergoing invitro fertilization (IVF) between 2008 and 2012 using autologous or donated eggs who had a singleton pregnancy delivered from the 24th week onward. Fresh embryo transfer (ET) or frozen-thawed ET in women undergoing IVF. Primary outcome birthweight, and secondary outcomes gestational age at delivery, small for gestational age, mode of delivery, and perinatal mortality. In the autologous egg population, newborns from the fresh ET group had lower birthweight than the frozen-thawed ET group (3,152.9 ± 545.5g and 3,343.2 ± 532.3g, respectively), and this difference persisted even after adjusting for confounding factors, and the newborns had a higher risk of being small for gestational age (SGA). In contrast, among egg-donor recipients undergoing ET, the mean birthweight did not differ between the groups (3,165 ± 604.15g and 3,143.60 ± 604.21g in the fresh and frozen-thawed ET groups, respectively); however, in the adjusted regression model birthweight was statistically significantly higher in the fresh ET group than the frozen-thawed ET group. The risk of SGA remained comparable between the fresh versus frozen-thawed ET groups. We observed no statistically significant differences in perinatal mortality between groups either in the autologous egg population or in the donor recipient group. Perinatal outcomes are negatively affected by COH and not affected by the vitrification process.

Use of Utrogestan during controlled ovarian hyperstimulation in normally ovulating women undergoing in vitro fertilization or intracytoplasmic sperm injection treatments in combination with a “freeze all” strategy: a randomized controlled dose-finding study of 100 mg versus 200 mg

To compare the clinical characteristics in a Utrogestan and hMG protocol with the use of different doses of Utrogestan in normally ovulating women undergoing invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments. Prospective controlled study. Tertiary-care academic medical center. A total of 150 infertile patients undergoing IVF/ICSI treatments. Utrogestan and hMG were administered simultaneously beginning on cycle day 3. The dose of Utrogestan was 100mg/d in the study group and 200mg/d in the control group. When the dominant follicles reached mature, 0.1mg GnRH agonist was used for trigger. Viable embryos were cryopreserved in both protocols for later transfer. The primary outcome measure was the incidence of premature LH surge. Secondary outcomes included the embryo results and clinical pregnancy outcomes. Consistent LH suppression was achieved during controlled ovarian hyperstimulation with Utrogestan at 100mg, and the number of patients with profound LH suppression (LH <1.2 IU/L) in the low-dose group was significantly less than that in the high-dose group. The number of oocytes retrieved in the low-dose group was similar to that in the high-dose group (9.87 ± 5.77 vs. 10.25 ± 5.43). No significant differences were observed in the number of mature oocytes, viable embryos, clinical pregnancy rate, or implantation rate. Utrogestan at 100mg is as effective as Utrogestan at 200mg in reducing premature LH surge during controlled ovarian hyperstimulation. ChiCTR-OOC-14005277.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)-for ovarian stimulation in women undergoing invitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. The mean total treatment costs were estimated as €5664 for follitropin alfa (95%UI €5167-6151), €5990 for hp-HMG (95%UI €5498-6488) and €5760 for uFSH (95%UI €5256-6246). The probability of a live birth was estimated at 36.1% (95%UI 27.4-44.3%), 33.9% (95%UI 26.2-41.5%) and 34.1% (95%UI 25.9-41.8%) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5% that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Comparison of in vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes in Patients receiving Recombinant Human Luteinizing Hormone vs Human Menopausal Gonadotropin Supplementation

ABSTRACTObjectivesTo compare the outcome of recombinant human luteinizing hormone (rh-LH) and human menopausal gonadotropin (hMG) supplementation in women undergoingin vitrofertilization/ intracytoplasmic sperm injection (IVF/ICSI) with recombinant follicle stimulating hormone (FSH) in the long gonadotropinreleasing hormone (GnRH) agonist stimulation protocol.Materials and methodsIt was a retrospective analysis of the case records of 90 consecutive women who underwent nondonor IVF/ICSI cycle with long GnRH agonist. All women received recombinant FSH on day 2/3 of the programming cycle. When the level of LH was &lt; 0.5 mIU/mL during any phase of stimulation, then addition of LH either as rh-LH or hMG is given along with recombinant FSH.ResultsThe number of oocytes collected, the number of oocytes in metaphase II (MII), and fertilization rate were similar in both groups. In addition, the mean number of embryos produced per cycle and the mean number of frozen embryos per cycle were similar in both groups. The cost of gonadotropin is similar in both groups. The ongoing pregnancy rate at 12 weeks was 20.4% after rh-FSH + hMG and 29.2% after rh-FSH + rh-LH (p-value = 0.092).ConclusionSupplementing recombinant FSH with recombinant LH (rh-LH) when compared with hMG does not show statistically significant increase in pregnancy rates. However, this study was a pilot venture to introduce the rh-LH into our practice and further randomized study is required to substantiate its use in assistive reproductive technology.How to cite this articleUsha Rajinikanthan DB, Balasubramanyam S, Varma T. Comparison ofin vitroFertilization/Intracytoplasmic Sperm Injection Outcomes in Patients receiving Recombinant Luteinizing HormonevsHuman Menopausal Gonadotropin Supplementation. Int J Infertil Fetal Med 2016; 7(3):77-81.

Future research and developments in hysteroscopy

Hysteroscopy has become an important tool to evaluate intrauterine pathology. In most cases, the pathology can be diagnosed and treated in the office or outpatient setting. The ability to use normal saline as a distending medium allows the procedure to be performed using bipolar energy. During hysteroscopic myomectomy, visualization can remain unobstructed with the use of a hysteroscopic morcellator. Its use is also associated with decreased operating time. The use of Essure(®) to block the proximal fallopian tube by a hysteroscopic approach is an approved procedure for tubal sterilization. However, it has been increasingly used to prevent hydrosalpinx fluid from entering the uterine cavity in women undergoing invitro fertilization. The hysteroscopic approach has also been used to treat a variety of conditions such as treatment of interstitial pregnancy, caesarean scar pregnancy and retained placenta. However, the number of cases is still relatively small, and no randomized trial has ever been conducted. One of the potentially important developments is the use of falloposcopy to obtain distal tubal cytology as a screening for ovarian cancer. The technique remains to be refined.