Improvement In Clinical Pregnancy Rate Research Articles

P-407 Exploring the effectiveness of tailoring estradiol supplementation duration to mimic the natural cycle length in artificial endometrial preparation for frozen embryo transfer cycles

Abstract Study question Is an estrogen supplementation duration similar in length to the follicular phase of a natural cycle associated with a better clinical pregnancy rate? Summary answer An estradiol supplementation duration, which is proportional to the natural follicular phase length, results in significantly better outcomes compared to shorter exposure durations What is known already The last decade witnessed a major increase in the use of single euploid frozen embryos. Artificial endometrial preparation (AEP) has proven to be effective to prepare the endometrium for implantation. However, several features of AEP need to be clarified mainly the duration of estrogen supplementation and until now no study took into consideration the difference between exogenous estrogen supplementation and the actual length of the follicular phase of each patient during AEP. Furthermore, most of the studies focused on upper limit of estrogen exposure while few considered the lower limit. Unfortunately, the results on pregnancy rates were mixed. Study design, size, duration 663 single euploid frozen embryo transfer cycles were included. Patients underwent vaginal ultrasound and hormonal blood measurement (Estradiol, Progesterone) on day 2 of their cycle. Estradiol valerate (4 mg the first 2 days then 6 mg daily, Orally) was started on the same day and another control was done around day 10. When triple lining pattern of the endometrium was seen, vaginal progesterone was initiated (800 mg daily) and SET was done after 120 hours. Participants/materials, setting, methods Patients with reported regular menstrual cycle (25-35 days) were included and the difference between estrogen supplementation and the actual follicular phase was calculated for each patient. Patients were sorted into 2 groups as follows: 231 women with normal interval (±2 days of follicular phase length), and 432 women with short interval (-3 days or shorter). Only the first single euploid embryo transfer cycles were analyzed for these patients. Main results and the role of chance Whereas patients had similar characteristics in both groups, the corresponding clinical pregnancy rates in normal and short supplementation groups were 69.3% (160/231) and 64% (277/432), respectively. After balancing the groups for BMI, embryo quality and endometrial thickness with inverse treatment probability weighting, those who received estradiol supplementation proportional to their natural follicular phase length had significantly higher clinical pregnancy rates compared to those who received it for shorter durations (adjusted OR: 1.48, 95% CI: 1.16 – 1.89, P = 0.002). Serum estradiol levels were available for 523 cycles, the clinical pregnancy rate in those within the 1st quartile (<155pmol/L), 2nd to 3rd quartile (155 to 275pmol/L) and 4th quartile (>275pmol/L) were 70%, 64.7% and 63%. After adjusting for BMI and embryo quality, higher (>275pmol/L) (adjusted OR: 0.84, 95% CI: 0.53-1.32, P = 0.442) and lower(<155pmol/L) (adjusted OR: 1.37, 95% CI: 0.85-2.22, P = 0.202) estradiol levels were not significantly associated with clinical pregnancy. Limitations, reasons for caution The present study could not address the influence of very long estrogen supplementation on clinical pregnancy rate due to limited samples. Further prospective studies, including larger populations, are needed to confirm our findings Wider implications of the findings Our data indicate that mimicking individually the natural cycle regarding estrogen supplementation duration in AEP for single euploid embryo transfer cycles can produce significant improvement in clinical pregnancy rates. Trial registration number not applicable

SARS-CoV-2 infection is detrimental to pregnancy outcomes after embryo transfer in IVF/ICSI: a prospective cohort study.

To explore whether SARS-CoV-2 infection affects the pregnancy outcomes of assisted reproductive techniques (ART). A prospective cohort study recruited patients for embryo transfer from December 01, 2022, to December 31, 2022. All patients were closely followed up for SARS-CoV-2 infection after embryo transfer. The SARS-CoV-2 "diagnosed group" was defined as RNA or antigen-positive. The SARS-CoV-2 "suspected infection group" was defined as having apparent SARS-CoV-2 symptoms without an RNA or antigen test, while the "uninfected group" was defined as having a negative SARS-CoV-2 RNA or antigen test and no SARS-CoV-2 symptoms. A total of 1330 patients participated in the study, 687 of whom were in the SARS-CoV-2 diagnosed group, 219 in the suspected infection group, and 424 in the uninfected group. There was no significant difference in basic characteristics among the three groups. The clinical pregnancy rate was 68% in the SARS-CoV-2 diagnosed group, 63% in the uninfected group, and 51% in the suspected infection group (P < 0.001). The ongoing pregnancy rate was 58% in the SARS-CoV-2 diagnosed group, 53% in the uninfected group, and 45% in the suspected infection group (P < 0.001). Upon analyzing the factors influencing clinical pregnancy, it was found that suspected infection (odds ratio [OR] 0.618, 95% CI 0.444-0.862, P = 0.005) and the short time (≤ 22days) between embryo transfer and SARS-CoV-2 infection (OR 3.76, 95% CI 1.92-8.24, P < 0.001) were not conducive to clinical pregnancy. In addition, the concurrent presence of fever and dizziness/headache SARS-CoV-2 symptoms (OR 0.715, 95% CI 0.526-0.972, P = 0.032) decreased the clinical pregnancy rate. However, vaccination administered 2-3 times (OR 1.804, 95% CI 1.332-2.444, P < 0.001) was associated with an improvement in clinical pregnancy rate. This prospective cohort study shows that SARS-CoV-2 infection in a short period of time after embryo transfer is not conducive to clinical pregnancy. Reproductive physicians should advise patients to avoid SARS-CoV-2 infection shortly after embryo transfer. Meanwhile, women should be encouraged to vaccinate at least 2-3 times before embryo transfer or pregnancy.

Intrauterine perfusion of dexamethasone improves pregnancy outcomes in recurrent reproductive failure patients with elevated uterine natural killer cells. A retrospective cohort study

AbstractObjectiveTo determine the effect of intrauterine perfusion of dexamethasone (DXM) on pregnancy outcomes in recurrent reproductive failure (RRF) patients with elevated uNK cells.MethodsThis retrospective cohort study included 132 RRF patients with elevated uNK cells: 56 patients received DXM treatment and 76 patients refused it in the frozen‐thawed embryo transfer cycles. To determine the efficacy of intrauterine perfusion of DXM, multivariate logistic regression models and diagnosis‐based subgroup analysis were performed. We also compared the pregnancy outcomes of patients with different responsiveness to DXM treatment.ResultsIntrauterine perfusion of DXM significantly improved clinical pregnancy rate (aOR: 3.188, 95% CI: 1.395–7.282, P = .006) and live birth rate (aOR: 3.176, 95% CI: 1.318–7.656, P = .010) in RRF patients with elevated uNK cells, but there was no significant association with miscarriage rate. Subgroup analysis revealed that intrauterine perfusion of DXM in patients with recurrent implantation failure (RIF) showed significant improvement in clinical pregnancy rate (aOR: 6.110, 95% CI: 1.511–24.713, P = .011) and live birth rate (aOR: 9.904, 95% CI: 1.963–49.968, P = .005), but there was insufficient evidence of benefit in recurrent pregnancy loss (RPL) patients. Additionally, uNK cell levels dropped to normal range was achieved in only 35.90% of RRF patients after DXM treatment, no significant difference was found in pregnancy outcomes among patients with different responsiveness to DXM treatment (all P &gt; .05).ConclusionIntrauterine perfusion of DXM was a promising and effective treatment to enhance clinical pregnancy rate and live birth rate in RRF women with abnormally elevated uNK cells, and RIF patients are more likely to benefit than RPL patients.

Effect of Micronutrients and L-Carnitine as Antioxidant on Sperm Parameters, Genome Integrity, and ICSI Outcomes: Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

The evaluation of sperm DNA integrity is recommended in the sixth edition of the 2021 World Health Organization guidelines. Oxidative stress has been identified as a crucial factor leading to genome decay, lipid peroxidation, and nucleoprotein oxidation. This double-blind, placebo-controlled clinical trial aimed to assess the effect of oral antioxidant treatment (Fertilis), which contains L-carnitine and some micronutrients, in the improvement of conventional sperm parameters, sperm DNA integrity and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. A total of 263 participants were enrolled and randomly divided into two groups: 131 participants received the antioxidant treatment, while 132 participants received a placebo. The male partners in both groups underwent the antioxidant treatment or the placebo for a duration of three months. For each participant, we performed a hormonal test, an infectious test, a spermogram, a TUNEL assay for sperm DNA fragmentation, a toluidine blue staining for sperm DNA decondensation, and an IVF/ICSI procedure. Sperm characteristics analysis (volume, count, motility, and vitality), sperm DNA fragmentation, and sperm DNA decondensation were assessed and compared to the results preceding the antioxidant treatment. The study outcome revealed a significant decrease in the DNA fragmentation index and a significant increase in sperm motility after 3 months of treatment (p = 0.01 and p = 0.02, respectively). Additionally, a significant improvement in clinical pregnancy rate (p = 0.01) and life birth rate (p = 0.031) was observed. No significant changes were observed in conventional sperm parameters (volume, count, and vitality) or sperm DNA decondensation (SDI). Antioxidant therapy has a beneficial impact on achieving pregnancy, whether through spontaneous conception or assisted reproductive procedures (ART).

A decennial cross-sectional review of assisted reproductive technology in a Tertiary Hospital in Southwest Nigeria

BackgroundThe World Health Organization recommends that Assisted Reproductive Technology be complementary to other ethically acceptable solutions to infertility. Whereas fertility centres are increasing in number in urban regions of Africa, published reports of their performance are sparse. We present a 10-year review of assisted reproductive technology performed in a public tertiary centre in Lagos, Nigeria.MethodsThis was a hospital-based, retrospective, cross-sectional review of 604 women, over a 10-year period that had in-vitro fertilization or in-vitro fertilization with intra-cytoplasmic sperm injection at the Institute of Fertility Medicine, Lagos State University Teaching Hospital. Data obtained were expressed in descriptive statistics and Pearson correlation was used to determine the strength of linear relationship between two continuous variables at a significance level of p < 0.05.ResultsThe mean age of the women was of 37.7 ± 6.2 years and 89.7% had no previous parous experience. About 27.2% of the male partners had normal seminal fluid parameters while 4.6% had azoospermia. Median serum follicle stimulating hormone of the women was 8.1 IU/L and median serum anti-mullerian hormone was 6.3 pmol/L. There was weak positive correlation between age and serum follicle stimulating hormone (r = 0.306, p < 0.001); weak negative correlation between age and serum anti-mullerian hormone (r = -0.48, p < 0.001) and very weak correlation between body mass index and serum follicle stimulating hormone (r = 0.173, p = 0.011). In-vitro fertilization and intra-cytoplasmic sperm injection was the method of fertilization used in 97.4% of the cases and 81.8% of embryos formed were of good quality. Most women (94.5%) had 2 embryos transferred and 89.9% had day-5 embryo transfer done. About 1 in 4 of the women (143/604, 23.7%) had clinical pregnancy and 49.7% of women who got pregnant had delivery of a live baby at term while 11.9% had preterm delivery of a live baby.ConclusionDespite increasing use and success of assisted reproductive technology in south-western Nigeria, there is room for improvement in clinical pregnancy rates and live birth rates post- assisted reproductive technology. Complication rates are desirably low.

Endometrial scratching during hysteroscopy in women undergoing in vitro fertilization: a systematic review and meta-analysis.

Endometrial scratching (ES) during hysteroscopy before embryotransfer (ET) remains doubtable on whether it benefits the reproductive outcomes. The optimal technique is not clear and repeated implantation failure as a challenging field in in vitro fertilization (IVF) seems to be the springboard for clinicians to test its effectiveness. Medline, PMC, ScienceDirect, Scopus, CENTRAL, Google Scholar were searched from their inception up to April 2023 for studies to evaluate the effectiveness of adding endometrial scratching during hysteroscopy before ET. The initial search yielded 959 references, while 12 eligible studies were included in the analyses, involving 2,213 patients. We found that hysteroscopy and concurrent ES before ET resulted in a statistically significant improvement in clinical pregnancy rate (CPR) [RR = 1.50, (95% CI 1.30-1.74), p < 0.0001] and live birth rate (LBR) [RR = 1.67, (95% CI 1.30-2.15), p < 0.0001] with no statistically significant difference on miscarriage rate [RR = 0.80 (95% CI 0.52-1.22), p = 0.30]. Our meta-analysis suggests that hysteroscopy with concurrent ES may be offered in IVF before ET as a potentially improving manipulation. Future randomized trials comparing different patient groups would also provide more precise data on that issue, to clarify specific criteria in the selection of patients. PROSPERO (CRD42023414117).

Does Endometrial Compaction Predict Clinical Pregnancy Rate after Cleavage Stage Frozen Embryo Transfer?

Objectives: This study aimed to determine the relationships between endometrial compaction and pregnancy outcome in patients receiving artificial endometrial preparation for frozen embryo transfer (FET) cycles. Materials and Methods: This prospective cohort study was performed in a university-affiliated fertility clinic from March 2020 to March 2021. The eligible women undergoing their first or second FET cycle and having the top grading cleavage stage embryos were enrolled. All patients received the same endometrial preparation regime. The alteration in endometrial thickness (EMT) between the day of progesterone initiation and the day of embryo transfer (ET) was measured using consecutive transvaginal sonography. The patients were divided into three groups based on the percentage of endometrial compaction (i.e., the difference of EMT at end of the estrogen-only phase and after three days of progesterone administration (ET day) divided by the EMT on the terminal day of the estrogen-only exposure). Results: Overall, 300 eligible women were evaluated and only 27.3% (82/300) of the studied cycles showed ≥5% compaction, whereas 72.6% (218/300) either expanded or showed minimal compaction. The clinical and ongoing pregnancy rates in group 2 (any expansion) were significantly higher than those in groups 1 and 3 (P=0.002 and P=0.01, respectively). Multivariable logistic regression test indicated that the cycles with any expansion in ET were independently associated with 3.1 times improvement in clinical pregnancy rate in comparison to those with any compaction (P=0.002). Conclusion: Gross endometrial compaction occurred in one-third of FET cycles with no significant positive effect on pregnancy outcomes after cleavage-stage ET.

To curette or not to curette; efficiency of oocyte retrieval technique.

Follicular curetting is the gentle and rapidly rotating movement of the aspiration needle in a clockwise and counterclockwise fashion. The aim of our study is to assess this retrieval technique comparing cycle and pregnancy outcomes between curetting and non-curetting. This was a retrospective review of 817 patients that underwent oocyte retrieval at our fertility center from January 1st, 2016 until August 31st, 2019. All patients enrolled in the study underwent standard ovarian stimulation protocols. Three physicians routinely utilized follicle curetting during oocyte retrieval, while a fourth physician did not curette. Retrievals and embryo transfers were performed based on a rotating physician schedule. Retrievals that were performed using a curetting technique had a significantly higher number of total oocytes retrieved 12.4 ± 8.1 vs 10.7 ± 7.5 (p = 0.01), and number of M2 oocytes retrieved 8.1 ± 6.4 vs 6.9 ± 6.0 (p = 0.03), resulting in an increased M2 oocyte yield 63.7% ± 41.3 vs 50.9% ± 30.6 (p = 0.0001). These patients also had a significant increase in clinical pregnancy rate per retrieval 55 vs 41% (p = 0.0016), live birth rate per retrieval 42 vs 34% (p = 0.04) and with no significant difference in multiple gestations or OHSS. A significant improvement in clinical pregnancy rates and live birth per retrieval was detected in patients undergoing curetting. These patients had more embryos frozen, leading to more transfers and more successful pregnancies.

Does Adenomyosis Influence ICSI Clinical Outcome? A Systematic Analysis and Impact of GnRH Agonist Pretreatment for Women with Adenomyosis in ICSI-FET Cycle: A Retrospective Cohort Study.

To evaluate the impact of adenomyosis on pregnancy outcome in ICSI/FET cycles and the beneficial effect of GnRH agonist pretreatment, conservative surgery or combination therapy on pregnancy outcome. This is a retrospective cohort study where 613 ICSI cycles done in the period from Jan 2018 to Dec 2020 in Sudha infertility centre, Erode were analyzed. Study populations include 235 women with adenomyosis undergoing ICSI/FET cycle. Overall, the outcome in terms of clinical pregnancy rate, miscarriage rate, live birth date and ongoing pregnancy rate was lower in women with adenomyosis following ICSI/FET cycles. We found significant improvement in clinical pregnancy rate who had pretreatment with GnRH agonist, conservative surgery or combination therapy. Adenomyosis as such has detrimental effect on ICSI clinical outcome. Pretreatment with GnRH agonist and conservative surgery and GnRH agonist long protocol could be beneficial. Further large scale prospective comparative studies are needed to confirm this result.

Autologous platelet-rich plasma to prevent a thin endometrium in patients undergoing clomiphene citrate therapy: a pilot prospective self-controlled trial

Objectives: To explore the efficacy of intrauterine infusion of autologous platelet-rich plasma (PRP) in infertile ladies as an adjuvant to clomiphene citrate (CC) in ladies with previous CC failure attributed to a thin endometrium (≤ 7 mm). Design: A pilot prospective self-controlled trial. Patients and methods: The study included thirty anovulatory PCOS women with CC failure for 3 cycles with a thin endometrium (7 mm). All patients underwent ovarian stimulations for 2 cycles; 1) Control cycle: 30 women received CC alone and one got pregnant and 2) Study cycle;29 women received CC plus an intrauterine infusion of PRP. Main endpoints included the comparison of the endometrial thickness (ET) and endometrial vascularity pattern by power Doppler on the day of hCG injection between both treatment cycles. Results: There was a statistically significant increase in the endometrial thickness on the day of hCG injection with CC plus PRP compared to CC alone (8.98 ±1.31 vs, 5.8 ±1.2; p < 0.0001). There was a significant improvement in the endometrial blood flow with the use of PRP (p= 0.00004). The pregnancy rate is significantly higher in the PRP cycles compared to control cycles (7 pregnancies (24.14%) vs. one pregnancy (3.3%) respectively; p = 0.0257) Conclusion: Intrauterine infusion PRP seems to be a promising adjuvant to increase endometrial thickness and endometrial blood flow with subsequent improvement in clinical pregnancy rate in ladies with CC failure due to thin endometrium

Dual-trigger improves the outcomes of in vitro fertilization cycles in older patients with diminished ovarian reserve: A retrospective cohort study.

BackgroundDual-trigger for final oocyte maturation has been applied on the women with poor ovarian response or diminished ovarian reserve. However, the results were controversial. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the effectiveness of dual-trigger for final oocyte maturation on the in vitro fertilization (IVF) outcomes of patients who fulfill the POSEIDON group 4 criteria.MethodsThis retrospective cohort study investigated 384 cycles fulfilling the POSEIDON group 4 criteria. The patients underwent IVF treatment using the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study group contained 194 cycles that received dual-trigger (human chorionic gonadotropin [hCG] plus GnRH-agonist) for final oocyte maturation. The control group included 114 cycles where final oocyte maturation was performed with only hCG. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared.ResultsBaseline characteristics were similar between the dual trigger group and the control group. In terms of IVF outcomes, the dual trigger group demonstrated significantly higher number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos, and top-quality day-3 embryos. A statistically significant improvement in clinical pregnancy rate and live birth rate was also observed in the dual trigger group.ConclusionsOur data suggests that dual trigger for final oocyte maturation might improve clinical pregnancy rates and live birth rates of IVF cycles in patients fulfilling the POSEIDON group 4 criteria.

Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial

To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures. A nonblinded multicenter randomized clinical trial. Fertility clinics. Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153). Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation. Clinical pregnancy rate and prenatal and birth data. There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86-1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05-2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups. Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups. NCT01963819.

Hysterosalpingography prior to the gonadotropin stimulated intrauterine insemination improvesclinical pregnancy rates in women with unexplained infertility

Gonadotropin stimulated intrauterine insemination (IUI) cycles performed following one month after hysterosalpingography (HSG) are associated with improvement in clinical pregnancy rates in unexplained infertile couples. A retrospective cohort study was performed between 2008 and 2014. A total of 92 unexplained infertile couples undergoing their first cycle IUI stimulated by gonadotropins were included in the analysis. Participants were classified into two groups according to IUI cycles performed one month (Group A, n = 25 cycles) or longer than one month (Group B, n = 67 cycles) after the HSG procedure. The overall clinical pregnancy rate was found as 25% (23 clinical pregnancies / 92 cycles). Clinical pregnancy rate was 44 % (11/25) for Group A and 17.9 % (12/67) for Group B. In Group A, there were significantly higher clinical pregnancy rates compared to Group B (OR: 3.6, 95% CI, 1.3-9.8; p = 0.012). It has been demonstrated that fertility improving effect of HSG was most prominent in the first six months after procedure. Likewise, in gonadotropin stimulated IUI cycles performed following one month after HSG, there seems to be an improvement in pregnancy rates in unexplained couples. In unexplained cases, it may be a reasonable approach to plan IUI cycles in the first month after HSG in clinical practice.

Will intracytoplasmic morphologically selected sperm injection replace intracytoplasmic sperm injection in cases of severe oligo-astheno-teratozoospermia?

Objective The aim of the study was to compare between intracytoplasmic morphologically selected sperm injection (IMSI) and conventional intracytoplasmic sperm injection (ICSI) as regards laboratory and clinical outcomes in couples with severe oligo-astheno-teratozoospermia (OAT). Design This was a prospective, nonrandomized, controlled clinical trial. Setting The study was conducted in the Agial ICSI/IVF Center. Materials and methods A total of 1729 couples with severe OAT were enrolled: 1356 couples were submitted to routine ICSI (group I) and 373 couples were submitted to IMSI (group II) after they had been counselled about the possible role of the IMSI technique in increasing pregnancy rates. For IMSI, spermatozoa were selected at 6600× magnification using an inverted microscope. For conventional ICSI, spermatozoa were selected at 400× magnification. Main outcome measures Laboratory (fertilization rate, embryo quality, number of embryos transferred) and clinical outcomes (clinical pregnancy rate) were compared between the two groups. Both groups were comparable regarding the number of mature (MII) oocytes collected (P=0.36) and the total number of embryos transferred (P=0.202). No statistically significant difference was observed between the two groups regarding rates of fertilization (P=0.946), with a mean±SD of 63.47±25.15% in group I and 64.69±22.66% in group II. However, a statistically significant difference (P<0.001) was present regarding clinical pregnancy rates, 44 versus 57% in groups I and II, respectively. There was a lower number of cycles with no embryo transfer in the IMSI group versus the ICSI group (4.3 vs. 6.7%), but the difference was statistically insignificant (P=0.086). Major conclusion Our results suggest that IMSI provides a significant improvement in clinical pregnancy rates compared with ICSI in couples with severe OAT.

Effective treatment protocol for poor ovarian response: A systematic review and meta-analysis.

Poor ovarian response represents an increasingly common problem. This systematic review was aimed to identify the most effective treatment protocol for poor response. We searched MEDLINE, EMBASE, and The Cochrane Library from 1980 to October 2015. Study quality assessment and meta-analyses were performed according to the Cochrane recommendations. We found 61 trials including 4997 cycles employing 10 management strategies. Most common strategy was the use of gonadotropin-releasing hormone antagonist (GnRHant), and was compared with GnRH agonist protocol (17 trials; n = 1696) for pituitary down-regulation which showed no significant difference in the outcome. Luteinizing hormone supplementation (eight trials, n = 847) showed no difference in the outcome. Growth hormone supplementation (seven trials; n = 251) showed significant improvement in clinical pregnancy rate (CPR) and live birth rate (LBR) with an odds ratio (OR) of 2.13 (95% CI 1.06–4.28) and 2.96 (95% CI 1.17–7.52). Testosterone supplementation (three trials; n = 225) significantly improved CPR (OR 2.4; 95% CI 1.16–5.04) and LBR (OR 2.18; 95% CI 1.01–4.68). Aromatase inhibitors (four trials; n = 223) and dehydroepiandrosterone supplementation (two trials; n = 57) had no effect on outcome.

Uterine flushing with supernatant embryo culture medium in vitrified warmed blastocyst transfer cycles: a randomized controlled trial

Does transfer of supernatant embryo culture fluid (stimulation of endometrial embryo transfer - SEET) prior to vitrified warmed blastocyst transfer result in better clinical pregnancy and live birth rates than direct vitrified warmed blastocyst transfer? This randomized controlled trial compared SEET group and direct transfer group (control) in 60 women undergoing vitrified warmed blastocyst transfers. The duration of the study was 3 years. The patients were undergoing vitrified warmed blastocyst transfer at university level infertility centre. Sixty women were randomized to SEET (n = 30) or control (n = 30). Data was available for analysis from all the 30 women in the SEET group and 30 women in the control group. There were no drop outs in the trial. The implantation rate was significantly lower in the SEET group compared to the control group (27 vs. 44 %, P = 0.018). The clinical pregnancy rates were similar in both the groups (47 vs. 53 %) but the live birth rate was also significantly lower in SEET group (23 vs. 50 %, P = 0.03). The sample size based on clinical pregnancy rates was small and hence not adequately powered to detect differences in live birth rates. Lack of blinding leading to possible bias cannot be ruled out. There was no evidence of an improvement in clinical pregnancy rate following SEET in vitrified warmed blastocyst transfer compared to direct transfer.

The role of seminal plasma for improved outcomes during in vitro fertilization treatment: review of the literature and meta-analysis.

There is a growing body of evidence surrounding the role played by seminal plasma in human implantation. Seminal fluid contains several proteins that interact with cervical and uterine epithelial cells inducing active immune tolerance. We sought to answer the study question: Does exposure to seminal plasma improve pregnancy outcomes in women undergoing IVF? Randomized controlled trials (RCTs) were searched for via MEDLINE, EMBASE, the Cochrane Library, National Research Register, ISI conference proceedings, ISRCTN register and Meta-register, from 1966 to December 2013. Search terms included: 'seminal plasma', 'seminal fluid', 'sexual intercourse', 'IVF', 'ICSI', 'ART', 'pregnancy rate', 'implantation', 'embryo transfer' and 'live birth'. This analysis included all RCTs comparing the outcome of IVF treatments in patients exposed to seminal plasma near the time of oocyte pickup (OPU) or embryo transfer (ET) with that of placebo controls or controls with no exposure to seminal plasma. The main intervention was exposure to seminal plasma around the time of OPU or embryo transfer during an IVF cycle. The main outcomes were clinical pregnancy and live birth/ongoing pregnancy rates. Data were collected by two independent authors and statistically pooled via meta-analysis following intention to treat and per protocol principles using RevMan (v5.2.10). I(2) statistic, forest plots and chi-squared heterogeneity tests were used. In total 2204 patients were included in seven RCTs. Meta-analysis revealed a statistically significant improvement in clinical pregnancy rate (RR 1.23, 95% CI 1.06-1.42, P = 0.006) by intention to treat. Per protocol analysis also revealed a statistically significant improvement in clinical pregnancy rate (RR 1.24, 95% CI 1.07-1.43, P = 0.003). There was no statistically significant improvement seen for the outcome of ongoing pregnancy/live birth rate, but the available data were very limited. The methodology and quality of the studies were variable. There are significantly improved outcomes when women are exposed to seminal plasma around the time of ovum pick-up or embryo transfer, with statistical significance for clinical pregnancy but not for ongoing pregnancy/live birth rates being achieved. This meta-analysis is limited by the small number of studies of variable methodology. Further research is required to determine the effect on live birth rate; however, this meta-analysis indicates a significantly improved clinical pregnancy rate and a potential method for improving IVF outcomes.

Significant improvement in pregnancy rates following frozen embryo transfers when combined with microarray-comparative genomic hybridization (aCGH)

ObjectiveThere is a growing body of evidence that embryo transfer (ET) of vitrified blastocysts in an unstimulated cycle improves implantation rates due to a more receptive uterine environment. Evidence is also growing that 24-chromosome screening to select euploid embryos improves implantation rates. This study looks at the effect of combining these two procedures on pregnancy rates by comparing outcomes of fresh versus warmed transfers of blastocysts that were screened by aCGH and those that were not.DesignRetrospective data analysis at a private fertility clinic.Materials and Methods827 sequential, non-randomized, ET's performed over 11-months during 2012 – 2013 were evaluated. Fresh ET was performed at the blastocyst stage on patients with a mean age of 34.8 years. Warmed ET was performed in unstimulated cycles after blastocysts were vitrified then individually warmed using the Cryotop® method (Kitazato). Trophectoderm biopsy followed by aCGH testing (Reprogenetics) was performed on Day 5 or 6 on patients with a mean age of 38.6 years.ResultsSignificant improvement in clinical pregnancy (CP) was demonstrated in all warmed ETs following aCGH testing (∗p<0.0216). A trend in CP increase was found for both: warmed ET vs. fresh ET without testing (^p<0.0858) and for warmed ET vs. fresh ET following aCGH testing (#p<0.0520).ConclusionSignificant improvement in clinical pregnancy rates may be obtained by taking advantage of the ability of A) blastocysts to survive trophectoderm biopsy for aCGH testing, B) vitrification/warming methodology being successfully applied to biopsied blastocysts, and C) for warmed, euploid embryos to be transferred into an unstimulated uterine environment that is more receptive to embryo implantation. ObjectiveThere is a growing body of evidence that embryo transfer (ET) of vitrified blastocysts in an unstimulated cycle improves implantation rates due to a more receptive uterine environment. Evidence is also growing that 24-chromosome screening to select euploid embryos improves implantation rates. This study looks at the effect of combining these two procedures on pregnancy rates by comparing outcomes of fresh versus warmed transfers of blastocysts that were screened by aCGH and those that were not. There is a growing body of evidence that embryo transfer (ET) of vitrified blastocysts in an unstimulated cycle improves implantation rates due to a more receptive uterine environment. Evidence is also growing that 24-chromosome screening to select euploid embryos improves implantation rates. This study looks at the effect of combining these two procedures on pregnancy rates by comparing outcomes of fresh versus warmed transfers of blastocysts that were screened by aCGH and those that were not. DesignRetrospective data analysis at a private fertility clinic. Retrospective data analysis at a private fertility clinic. Materials and Methods827 sequential, non-randomized, ET's performed over 11-months during 2012 – 2013 were evaluated. Fresh ET was performed at the blastocyst stage on patients with a mean age of 34.8 years. Warmed ET was performed in unstimulated cycles after blastocysts were vitrified then individually warmed using the Cryotop® method (Kitazato). Trophectoderm biopsy followed by aCGH testing (Reprogenetics) was performed on Day 5 or 6 on patients with a mean age of 38.6 years. 827 sequential, non-randomized, ET's performed over 11-months during 2012 – 2013 were evaluated. Fresh ET was performed at the blastocyst stage on patients with a mean age of 34.8 years. Warmed ET was performed in unstimulated cycles after blastocysts were vitrified then individually warmed using the Cryotop® method (Kitazato). Trophectoderm biopsy followed by aCGH testing (Reprogenetics) was performed on Day 5 or 6 on patients with a mean age of 38.6 years. ResultsSignificant improvement in clinical pregnancy (CP) was demonstrated in all warmed ETs following aCGH testing (∗p<0.0216). A trend in CP increase was found for both: warmed ET vs. fresh ET without testing (^p<0.0858) and for warmed ET vs. fresh ET following aCGH testing (#p<0.0520). Significant improvement in clinical pregnancy (CP) was demonstrated in all warmed ETs following aCGH testing (∗p<0.0216). A trend in CP increase was found for both: warmed ET vs. fresh ET without testing (^p<0.0858) and for warmed ET vs. fresh ET following aCGH testing (#p<0.0520). ConclusionSignificant improvement in clinical pregnancy rates may be obtained by taking advantage of the ability of A) blastocysts to survive trophectoderm biopsy for aCGH testing, B) vitrification/warming methodology being successfully applied to biopsied blastocysts, and C) for warmed, euploid embryos to be transferred into an unstimulated uterine environment that is more receptive to embryo implantation. Significant improvement in clinical pregnancy rates may be obtained by taking advantage of the ability of A) blastocysts to survive trophectoderm biopsy for aCGH testing, B) vitrification/warming methodology being successfully applied to biopsied blastocysts, and C) for warmed, euploid embryos to be transferred into an unstimulated uterine environment that is more receptive to embryo implantation.

Deleterious impact of propofol on in vitro fertilization. a prospective randomized trial

Propofol is widely used for anesthesia in oocyte transvaginal aspiration. In vitro studies on animal models have shown that propofol could be deleterious for fertilization and embryo development in a dose- and time-dependent manner. The purpose of this study was to analyse the potential negative effects of propofol on human in vitro fertilization outcomes. Prospective-double blind, randomized trial. 144 patients with more than four metaphase II oocytes retrieved were enrolled in this study and randomly separated. Two protocols of anesthesia were used. Group A: (GA, n=74) received intravenous (IV) propofol 2 mg/kg, midazolam 0.015 mg/kg and fentanyl 1 μg/kg. Group B: (GB, n=74) IV propofol 1.5 mg/kg, midazolam 0.05 mg/kg and fentanyl 1.5 μg/kg. Maintenance of anesthesia was achieved by intermittent IV bolus when required. Quantity of propofol, duration and quality of anesthesia, number of oocytes, embryo quality and pregnancy rate were evaluated. Mean doses of propofol were GA: 0.277 ± 0.080 mg/kg.min and GB: 0.195 ± 0.055 mg/kg.min (p< .01). No significant differences were found among anesthetics parameters, patient age, number of oocytes retrieved, fertilization rate and embryo quality in both groups. A significative difference was found in clinical pregnancy rate between groups (GA: 27.0% vs GB: 43.3%, p < .05). Our findings suggest that the administration of high doses of propofol produces a negative late effect on human embryo development. The use of lower doses of propofol and the consistent lower exposure of the oocytes to the drug, show an improvement in clinical pregnancy rate, maintaining quality of anesthesia and optimal postoperative recovery. According to our results, we postulate that the reduction of propofol could improve the results of in vitro fertilization treatments.

Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction

Subfertility is a condition found in up to 15% of couples of reproductive age. Gamete micromanipulation, such as intracytoplasmic sperm injection (ICSI), is very useful for treating couples with compromised sperm parameters. Recently a new method of sperm selection named 'motile sperm organelle morphology examination' (MSOME) has been described and the spermatozoa selected under high magnification (over 6000x) used for ICSI. This new technique, named intracytoplasmic morphologically selected sperm injection (IMSI), has a theoretical potential to improve reproductive outcomes among couples undergoing assisted reproduction techniques (ART). To compare the effectiveness and safety of IMSI and ICSI in couples undergoing ART. We searched for randomised controlled trials (RCT) in electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); in addition, we handsearched the reference lists of included studies and similar reviews. We performed the last electronic search on 8 May 2013. We considered only truly randomised controlled trials comparing ICSI and IMSI to be eligible; we did not include quasi or pseudo-randomised trials. We included studies that permitted the inclusion of the same participant more than once (cross-over or 'per cycle' trials) only if data regarding the first treatment of each participant were available. Two review authors independently performed study selection, data extraction, and assessment of the risk of bias and we solved disagreements by consulting a third review author. We corresponded with study investigators in order to resolve any queries, as required. The search retrieved 294 records; from those, nine parallel design studies were included, comprising 2014 couples (IMSI = 1002; ICSI = 1012). Live birth was evaluated by only one trial and there was no significant evidence of a difference between IMSI and ICSI (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.79 to 1.64, 1 RCT, 168 women, I(2) = not applicable, low-quality evidence). IMSI was associated with a significant improvement in clinical pregnancy rate (RR 1.29, 95% CI 1.07 to 1.56, 9 RCTs, 2014 women, I(2) = 57%, very-low-quality evidence). We downgraded the quality of this evidence because of imprecision, inconsistency, and strong indication of publication bias. We found no significant difference in miscarriage rate between IMSI and ICSI (RR 0.82, 95% CI 0.59 to 1.14, 6 RCTs, 552 clinical pregnancies, I(2) = 17%, very-low-quality evidence). None of the included studies reported congenital abnormalities. Results from RCTs do not support the clinical use of IMSI. There is no evidence of effect on live birth or miscarriage and the evidence that IMSI improves clinical pregnancy is of very low quality. There is no indication that IMSI increases congenital abnormalities. Further trials are necessary to improve the evidence quality before recommending IMSI in clinical practice.