Clinical Pregnancy Rate In Women Research Articles

Effect of vaginal/oral tadalafil on endometrial thickness in IVF patients: a double-blind, placebo controlled RCT: a pilot study.

To investigate the effect of tadalafil (a long working phosphodiesterase type 5 inhibitor) on the endometrial thickness, biochemical pregnancy rates and clinical pregnancy rates in women in an in vitro fertilization treatment. This study investigates the use of vaginal and oral administration of tadalafil. This is a prospective double-blind placebo-controlled randomized controlled trial with 58 patients in an in vitro fertilization treatment with a short antagonist stimulation protocol. The study population is divided into three equal groups comparing oral and vaginal administration of tadalafil to a control group. No significant difference in endometrial thickness and number of biochemical and clinical pregnancies was found between the three groups. This study could not show a significant benefit of administration of tadalafil. However, a trend towards more pregnancies in the group treated with oral tadalafil is seen, more research in specific subgroups is needed.

P-350 Endometrial receptivity analysis (ERA) and microbiome testing for recurrent implantation failure (RIF): a matched case control study

Abstract Study question Does the use of ERA, EMMA (endometrial microbiome metogenomic analysis) or ALICE (analysis of infectious chronic endometritis) improve implantation rate and clinical pregnancy? Summary answer The use of ERA significantly improves the clinical pregnancy rate in women with recurrent implantation failure, no difference was observed for EMMA or ALICE. What is known already The ability of ERA to utilise endometrial tissue transcriptomics to detect asynchronous cycles is controversial. Retrospective studies have demonstrated significantly lower implantation rates for the non-receptive cohort and improved pregnancy rates by personalising the embryo transfer (pET). An RCT reported comparable clinical outcomes for pET and standard FET. There have also been multiple reports of the endometrium being dominated by Lactobacillus, prevalence of this species without bacterial vaginosis leads to positive outcomes in IVF. That said, there is a scarcity of good quality evidence to advocate the use of antibiotics and/or probiotics to treat dysbiosis or pathogens in the subfertile population. Study design, size, duration From Jan 2017 to August 2021 202 patients underwent one or more of ERA (n = 202), EMMA (n = 101), and/or ALICE (n = 97) at CARE Fertility UK. The cycle subsequent to the test was compared to 404 age matched control cycles. Participants/materials, setting, methods This study included patients from all 22 clinics across CARE Fertility UK. Rates of positive pregnancy test and clinical pregnancy were compared between patients with normal and abnormal test results using Chi-squared statistic. Binary logistic regression analysis and odds ratios were used to test for improvements in clinical outcomes by adjusting for the following covariates: age, BMI, parity, 2 or more previous implantation failures, donor eggs and frozen embryos. Main results and the role of chance ERA testing resulted in a normal result in 42.3% of patients, 30.6% were pre-receptive and 17% were early receptive. EMMA resulted in a normal result in 36% of patients, 22% were abnormal, 17% had ultra-low biomass and 25% mild dysbiosis. Only 4% of patients using the ALICE tested positive, therefore this was not included in any modelling due to low event rates. The implantation rate and clinical pregnancy rates showed no statistical significance between those with an abnormal result vs. those who had a normal test. When comparing those tested to matched controls and adjusting for the above covariates, the use of the ERA test was significantly associated with improved implantation rate (OR 3.08, 95% CI 1.57-6.03, p = 0.001) and clinical pregnancy rate (OR 2.7, 95% CI 1.38-5.28, p = 0.004). The use of the EMMA test did not improve implantation (OR 0.42, 95% CI 0.051-3.437, p = 0.418) or clinical pregnancy rate (OR 0.48, 95% CI 0.039-5.89, p = 0.566). When comparing those with an abnormal ERA (i.e. presumed intervention) to matched controls the ERA test was significantly associated with improved clinical pregnancy (OR 5.4, 95% CI 2.007-14.85, p < 0.001). On the other hand, EMMA was not associated with any improvements (p = 1.0). Limitations, reasons for caution The data collection process had limitations since minimal information was available for patients who underwent previous cycles at other clinics. The number of patients with receptive ERA and abnormal EMMA is small (n = 25) vs. those with a normal EMMA and ERA (n = 10). Therefore, a significant limitation is sample size. Wider implications of the findings ERA can be more confidently offered to patients and has been demonstrated to significantly improve clinical pregnancy rates. Further research is needed before we can determine whether EMMA or ALICE is a useful test, particularly when considering very few patients show evidence of chronic endometritis. Trial registration number Not applicable

High-sensitivity C-reactive protein levels and pregnancy outcomes in women with unexplained infertility after ovarian stimulation with intrauterine insemination in a multicenter trial

ObjectiveTo determine if chronic inflammation, assessed by basal high-sensitivity C-reactive protein (hs-CRP) levels, is associated with pregnancy outcomes in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination.DesignProspective cohort analysis of the Reproductive Medicine Network’s Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial.SettingMulticenter university-based randomized controlled trial.Patient(s)A total of 781 couples with unexplained infertility.Intervention(s)Secondary analysis.Main Outcome Measure(s)Adjusted risk ratios of live birth, clinical pregnancy, and pregnancy loss rates by hs-CRP levels.Result(s)Associations between hs-CRP levels and clinical pregnancy rates were not observed after adjustment for baseline body mass index. There were fewer live births among women with higher hs-CRP levels, although confidence intervals crossed 1.0. The risk of pregnancy loss was greater in women with increased hs-CRP levels (1–3 mg/L: risk ratio [RR], 1.67; 95% confidence interval [CI], 1.00–2.79; >3–10 mg/L: RR, 1.84; 95% CI, 1.06–3.20; and >10 mg/L: RR, 2.14; 95% CI, 1.05–4.36 compared to women with hs-CRP <1 mg/L).Conclusion(s)This investigation suggests that chronic inflammation may increase the risk of pregnancy loss but not impact the clinical pregnancy rate in women with unexplained infertility undergoing ovarian stimulation with intrauterine insemination. Associations between inflammation and pregnancy outcomes in women with infertility merit further investigation.Clinical Trial Registration Numberclinicaltrials.gov NCT01044862.

Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome

Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome

Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis

ABSTRACT Endometriosis is a common estrogen-dependent chronic inflammatory disease that leads to infertility in women of reproductive age. Perhaps infertility reflects the reduced expression of integrin αvβ3 and HOXA10 in endometriosis. Previous studies have shown that administration of letrozole, a non-steroidal aromatase inhibitor for cancer treatment, increased the clinical pregnancy rate in women with endometriosis, but the mechanisms remain to be determined. In this communication, a rat model of endometriosis was established. Animals were treated with letrozole at 2ug/kg of body weight, intragastric administration for 15 consecutive days. Letrozole increased the expression of αvβ3 and HOXA10 in the endometriosis model and endometrial receptivity. Abbreviations: WOI: window of implantation; RGD: Arg-Gly-Asp; HOX: homeobox; E2: estradiol; SPF: specific pathogen-free.

The Current Role of Induced Endometrial Trauma (Endometrial Scratch) in Women Undergoing Infertility Treatment.

Induced endometrial trauma, otherwise known as endometrial scratch is a simple technique that has been rapidly adopted into clinical practice, mainly for women having IVF treatment, in an attempt to increase pregnancy rates. The introduction of endometrial scratch followed early reports of improved clinical pregnancy rates in women with repetitive implantation failure after having the procedure and follows on from evidence from animal models in the early 20th century suggesting that mechanical trauma to the endometrium can induce decidual changes. Due to the ease and low cost of the procedure, it has been rapidly adopted as an add-on to fertility treatments, in many cases where evidence is still lacking. Despite the initial publication of a large number of studies that demonstrated encouraging improvements in pregnancy rates in women who underwent this procedure, these studies were mainly limited by the small sample sizes and heterogeneity of their study populations, leading to limited validity of the evidence provided by these studies. More recently, three large randomized controlled studies have been published that paint a different picture regarding the value of this procedure. This article explores the evolution of the evidence and the current state of endometrial scratch as an adjuvant therapy for women undergoing IVF treatment.

MILD OVARIAN STIMULATION WITH LOW DOSE R-FSH MAY BE AN EFFECTIVE STRATEGY FOR ENDOMETRIAL PREPARATION IN WOMEN WITH THIN ENDOMETRIUM UNDERGOING FROZEN-THAW BLASTOCYST TRANSFER IN OOCYTE DONATION PROGRAMS

To evaluate whether low dose ovarian stimulation enhances embryo implantation potential better than exogenous estrogen supplementation in women with thin endometrium undergoing frozen-thaw transfer (FET) in oocyte donation (OD) cycles. Phase 1: Fresh blastocyst transfer in 485 OD cycles during 2018-2020. Endometrial preparation was done by conventional exogenous estrogen supplementation from day5 (protocol A). Of these, 105 women had thin endometrium (< 7 mm) on day 14. Yet, fresh transfer was done since literature reports pregnancies in endometrium as thin as 3.7 mm. However, none of these 105 women conceived. Phase 2: Subsequent FET cycle of those 105 women. They were prospectively subjected to minimal stimulation protocol of 37.5 IU of r–FSH daily from d3 till day14 (protocol B). Endometrial thickness >7 mm was achieved in 95 women and blastocyst transfer was done. The remaining 10 women where adequate endometrial thickness was not attained, did not receive embryo transfer. All women, whether undergoing protocol A or B, received luteal phase support from day14 with injection micronized progesterone (100mg daily). Sr. B-hCG was measured on day 7 of blastocyst transfer and a value >50 mIU/ml was considered as positive indicator of pregnancy. Gestational sac with positive cardiac activity at week 6 confirmed implantation. Women with thin endometrium who had undergone Protocol A (n=105) were intercompared with those following Protocol B (n=95) for clinical outcomes. Endometrial thickness on day14 in women undergoing Protocol B was significantly higher as compared to those undergoing Protocol A (9.0 ± 2.0 mm vs. 5.3 ± 1.5; p = 0.0015). The endometrial echogenicity in Protocol B was also significantly enhanced (grade 2.9 ± 0.32) as against that in Protocol A (grade 2.4 ± 0.24; p = 0.0328). Similarly, on day of blastocyst transfer, the endometrial response showed a rising trend in endometrial thickness and gradation (11 ± 1.05 mm, pattern 3.9 ± 0.2) in Protocol B compared to protocol A women (6.5.0 ± 2.0 mm; grade 3.1 ± 0.5) respectively. Sr. E2 levels on day of transfer showed raised level in Protocol B compared to Protocol A (412 ± 31.0 pg/ml vs. 315 ± 49 pg/ml; P = 0.00136). None of the 105 women had achieved pregnancy in their fresh transfer cycles using Protocol A. However, in the subsequent FET cycle using Protocol B, out of 95 cycles, 24 resulted in clinical pregnancies (Pregnancy rate 25.3%) whereas 2 were ectopic pregnancies. Administration of low dose (37.5 IU) r-FSH boosts endometrial thickness and echo-pattern and significantly enhances clinical pregnancy rates in women with thin endometrium undergoing FET blastocyst transfer in OD cycles. This protocol may be followed not just for FET but fresh OD cycles too.

P–375 Intralipid supplementation in women with unexplained recurrent implantation failure and elevated uterine natural killer cell levels - A randomized placebo controlled trial

Abstract Study question Does intralipid supplementation in women with unexplained recurrent implantation failure (RIF) with elevated uterine natural killer cell (uNK) levels improve pregnancy outcomes during IVF? Summary answer Intralipid supplementation appears to improve clinical pregnancy rate in women with unexplained RIF with elevated uNK cell levels. What is known already The increased numbers of uNK cells in peri-implantation endometrium have been reported in women with recurrent miscarriage (RM) and RIF after IVF. However, reports are contradictory when it comes to correlation of increased numbers of uNK cells with pregnancy outcome. Current opinion suggests there is a potential for intralipid therapy in improving reproductive outcome, although data on live birth rate is very limited. No studies have assessed the effect of intralipid on IVF outcomes in RIF women based on elevated uNK cells. Identified studies have all used pNK cell testing as preferred diagnostic tool for analysis of NK cell levels. Study design, size, duration A randomized placebo controlled trial was conducted at Division of Reproductive Medicine at tertiary care institute. Thirty women with RIF and fifty fertile controls with age &amp;lt;35 years having regular menstrual cycles and no hormonal treatment in last 3 months were enrolled in the study from January 2019 to December 2020 for uNK cell testing. Randomization was done using random numbers and sealed envelopes. Only the subjects were masked and allocation concealment was done. Participants/materials, setting, methods Subjects included RIF 20–35 years, normal ovarian reserve, unexplained and tubal factors, normal karyotype and normal uterine cavity. Cut off for uNK cells was derived from fertile controls by immunohistochemical staining of CD56+ cells from midluteal endometrial biopsy sample. Subjects with elevated uNK cell levels were randomized during IVF to group A (Intralipid) or group B ( saline ). The infusion was repeated within one week of positive pregnancy test and then every 2 weeks. Main results and the role of chance The mean age and BMI were comparable between fertile control and study group(29.45±3.3 vs 31.17±3.3 years, 22.97±1.89 vs 23.21±2.2 kg/m2 ;p&amp;gt;0.05). The median uNK cell levels was 7%(used as cut off) in fertile controls and 13.5% in RIF. 18 women (60%, 18/30) with RIF who had elevated uNK cell level (&amp;gt;7%) were randomized. Four women were lost to follow up. The median age, BMI, number of previous failed cycles and duration of infertility were comparable between Group A(n = 7) and Group B(n = 7){30(IQR:27–31) vs 33(IQR:30–34)years, 22.7(IQR:21.08–24.4) vs 22.6(IQR:21.37–24.2)kg/m2, 2(IQR:2–3) vs 2(IQR:2–3), 8(IQR:7–8) vs 8(IQR:7–10)years}. The median FSH, AMH and AFC were 5.86(IQR:5.13–7.67)mIU/l, 2.4(IQR:2.16–6.12)ng/ml, 10(IQR:8–12) in Group A which were comparable with Group B {6.2(IQR:4.78–6.5)mIU/l, 4.8(IQR:2.67–6.25)ng/ml, 12(IQR:12–16) }. All patients underwent antagonist protocol. The clinical pregnancy rate was 57.14%(4/7) in group A which was significantly higher as compared to 28.6%(2/7) in group B(p &amp;lt; 0.05). None of the patients reported any side effects due to intralipid. Limitations, reasons for caution The limitation of present study is its small sample size. However, the study is currently recruiting more RIF patients, and these are the interim results of the same. More RCTs with larger sample size are required to assess the efficacy of intralipid in this specific subset of population. Wider implications of the findings: The present study suggests the beneficial effect of intralipid in women with unexplained RIF with elevated uNK cell levels in increasing the chemical and clinical pregnancy rate. However, ongoing pregnancy rate and live birth rate should be investigated further in this subset of population. Trial registration number CTRI/2019/01/017213

P–342 Are blastulation and clinical pregnancy rates in women with endometriomas different than those without?

Abstract Study question Does the presence of endometrioma during ovarian stimulation affect blastulation and clinical pregnancy rates (CPR)? Summary answer Blastulation rates were similar in women with endometrioma compared to women without. Likewise, CPR were comparable. What is known already Although relationship of endometriosis and subfertility is well-established, its mechanism is still under investigation. Decreased oocyte quality, resulting from anatomical and/or inflammatory factors is one of the prominent culprits. Most studies regarding endometriosis and oocyte quality are highly heterogeneous and effect of endometriosis on oocyte quality is yet to be determined. Blastulation is thought as a surrogate marker for oocyte quality. Thus, it may be possible that detrimental effect of the presence of endometrioma during ovarian stimulation can be indirectly assessed by blastulation. Study design, size, duration Records of all women who underwent assisted reproductive technology treatment at Koc University Hospital Assisted Reproduction Unit between 2016 and October 2020 were screened for this retrospective study. All women who had endometrioma(s) during ovarian stimulation were included in the study group (EG) (n = 71). They were matched with women diagnosed with tubal factor or unexplained infertility who underwent oocyte pickup within the same period to form the control group (CG) (n = 104). Participants/materials, setting, methods All women underwent antagonist or long protocol. All embryos were cultured until blastocyst stage regardless of the number of oocytes or embryos available. Size/location of endometriomas, number of oocytes retrieved, number of available blastocysts, positive pregnancy test per cycle and clinical pregnancy rate per cycle were recorded. Blastulation rate was calculated as number of available blasts divided by the number of metaphase-II oocytes. Embryos were transferred in a fresh or artificially prepared frozen-thawed cycle. Main results and the role of chance There were 71 women in EG and 104 women in CG, which included 30 women with tubal and 74 with unexplained infertility. Median endometrioma size was 26 mm(22–33). Twenty-three patients in EG had history of endometrioma excision (31.3%). Median age [35.0 years (31.0–39.0) vs 34 (32.0–36.0), p = 0.26] and serum AMH levels [1.8 (1.1 - 4.2) vs 2.3 (1.3 - 3.7) ng/dL, p = 0.91] were similar in EG and CG, respectively. Body mass index in kg/m2 [21.8 (20.2–24.6) vs 24 (21.5–27.9), p &amp;lt; 0.01] and infertility duration in years [2 (1–2.6) vs 3 (2–5), p &amp;lt; 0.01] were significantly lower in EG. Number of retrieved oocytes [8 (5–12) vs 12 (7–15.8), p &amp;lt; 0.01)] and metaphase-II oocytes [6 (4–10) vs 8.5 (6–12), p &amp;lt; 0.01] were lower in EG group compared to CG group. However, blastulation rate per MII oocyte were similar between the EG and CG [(0.25 (0.20–0.41) vs 0.30 (0.14–0.50), respectively, p = 0.58]. Adjusted analysis for age and number of MII oocytes revealed similar finding. Positive pregnancy test per cycle was similar at 53.5% vs 61.5% in EG and CG, respectively (p = 0.3). CPR were similar between the EG and CG (45% vs 58%, respectively, p = 0.10). Limitations, reasons for caution Retrospective design, lack of live birth information are the main limitations of our study. Wider implications of the findings: Presence of endometrioma during ovarian stimulation does not seem to adversely affect blastulation rates. While this is reassuring regarding oocyte quality, further research is required to assess its effect on live birth. Trial registration number Not applicable

P–747 Implementation of the ESHRE Congenital uterine anomaly classification into practice and clinical pregnancy outcomes at a Tertiary University Teaching Hospital Fertility department

Abstract Study question What’s the incidence of class U1-U6 CUAs in subfertile women? What’s the clinical pregnancy rate in women with the most common anomaly, a septate uterus? Summary answer The incidence of CUAs is 5.9% in our subfertile population, with a septate uterus (U2) being the most common abnormality in 4.2% of the population What is known already Congenital uterine anomalies (CUAs) are common. A systematic review suggested an estimated overall prevalence of 5.5% in an unselected population, 8.8% in the subfertile population, 13.3% in those with a history of recurrent miscarriage and 24.5% in those with a history of subfertility and recurrent miscarriage. A septate uterus (U2) is the most common CUA and is amenable to surgical intervention although at present there is a lack of evidence suggesting benefit in subfertile patients. Women with a septate uterus are known to have poorer reproductive outcomes, including reduced conception rate and increased first trimester loss. Study design, size, duration All patients referred to our department for subfertility had a 2D pelvic ultrasound scan as part of their baseline investigations. Since it was established in 2016, all patients with a suspected CUA based on clinical history and investigations, were referred to the clinic and data collected prospectively. Prior to this, women with suspected CUAs required a hysteroscopy or MRI scan for confirmation of diagnosis, often leading to long waiting lists and treatment delays. Participants/materials, setting, methods Out of the 4716 patients referred to the department for subfertility from 2016–2018, 302 women were referred to the 3D clinic due to suspicion of a CUA. Transvaginal 3D-ultrasound scan was performed and CUAs classified according to the ESHRE/ESGE working groups. Patients diagnosed with a septate uterus were given options of conservative versus surgical treatment, in the light of unclear benefits of hysteroscopic septum resection. Clinical pregnancy data were collected about this cohort. Main results and the role of chance Of the 302 women referred to the service, the uteri of 25 patients were unable to be assessed accurately, most commonly as the cavity was unclear due to a thin endometrium. The remaining 277 patients were classified as having the following CUAs; Normal (U0) 63 patients, Dysmorphic (U1) 5 patients, Septate (U2) 199 patients, Bicorporeal (U3) 6 patients and Hemi uterus (U4) 4 patients. No women were classified as having an aplastic uterus (U5) or unclassified (U6). Of the 199 women with a septate uterus, 15 women opted for surgical intervention, 143 women decided to have conservative management and 41 women were lost to follow up. The women who had hysteroscopic resection of the septum had a mean age of 35 years, 6/15 had primary subfertility and 6/15 had a history of recurrent miscarriage. The women who had conservative management had a mean age of 32.5 years, 100/143 had primary subfertility and 20/143 had a history of recurrent miscarriage. At present, 89/143 women who have had conservative management and 12/15 women who had surgical interventions have had a clinical pregnancy, 72/89 and 6/12 of these pregnancies were IVF/ICSI pregnancies respectively. Limitations, reasons for caution This is an observational study, these findings can be useful for patient counselling. However, ideally randomised controlled trials are needed as evidence for the different treatment options for the cohort of patients with septate uterus, which are largely lacking in the current literature, as their feasibility remains a challenge. Wider implications of the findings: Three-dimensional transvaginal ultrasonography clinics are cost-effective one-stop services, successfully providing a diagnosis and management plan in 92% of patients referred with a suspected CUA. They increase patient satisfaction by providing an opportunity to discuss risks in future pregnancies and reducing reliance on hysteroscopy and MRI scans. Trial registration number Not applicable

Hysteroscopic endometrial peeling as a different approach to endometrial scratching. Case series report

Study questionDoes hysteroscopic endometrial peeling improve reproductive outcomes in women with implantation failure? DesignIn this case series, 66 women underwent an hysteroscopic endometrial peeling and subsequently, a single frozen embryo transfer. ResultsAfter the exclusion of patients with intraoperative incidental findings, pregnancy was achieved in 63% (42/66) of the women who underwent hysteroscopic endometrial peeling and subsequently a single frozen embryo transfer, clinical pregnancy rate was observed in 57% (38/66) of the patients and, clinical pregnancy loss occurred in 10% (4/38). Conclusionthis novel surgical technique seems to increase implantation as well as clinical pregnancy rates in women with repeated implantation failure. We can hypothesize that the controlled and subtle degree of endometrial injury generated by the peeling generates an inflammatory cascade that enhances implantation.

An Overview of Systematic Reviews of Acupuncture for Infertile Women Undergoing in vitro Fertilization and Embryo Transfer.

Background: Currently, more and more subfertility couples are opting for combined acupuncture to improve the success rate of in vitro fertilization and embryo transfer (IVF-ET). However, the efficacy and safety of acupuncture in IVF-ET is still highly controversial.Objectives: The purpose of this overview is to summarize evidence of essential outcomes of systematic reviews (SRs) of acupuncture in IVF-ET and evaluate their methodological quality.Methods: We conducted a comprehensive literature search for relevant SRs in eight databases from inception to July 31, 2020, without language restriction. We evaluated the methodological quality of the included SRs by using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), which was the latest available assessment tool. The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. We assessed the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) score to determine the strength of evidence. We excluded the overlapping randomized controlled trials (RCTs) and performed a re-meta-analysis of the primary RCTs.Results: This review included 312 original RCT studies and 65,388 participants. By using AMSTAR-2, we found that the methodological quality of 16 SRs was critically low, because they had more than one critical weakness. Our reviews showed that although the GRADE for quality of evidence profile was suboptimal, acupuncture seemed to be beneficial in increasing the pregnancy rate. Our re-meta-analysis suggested that acupuncture was superior to sham acupuncture in improving the clinical pregnancy rate (CPR) of IVF-ET with substantial heterogeneity (RR = 1.31, 95% CI: 1.13–1.52, p = 0.0004, I2 = 66%). No statistical difference was observed regarding the outcomes of live birth rate (LBR), ongoing pregnancy rate (OPR), biochemical pregnancy rate (BPR), and miscarriage rate (MR) between two groups. When compared with no adjunctive treatment groups, acupuncture improved CPR (RR = 1. 25, 95% CI: 1.11–1.42, p = 0.0003) and OPR (RR = 1. 38, 95% CI: 1.04–1.83, p = 0.03). Acupuncture was more superior than no adjunctive treatment in reducing MR (OR = 1.42, 95% CI: 1.03–1.95, p = 0.03) and BPR (RR = 1.19, 95% CI: 1.02–1.37, p = 0.02).Conclusions: Although the evidence of acupuncture in IVF-ET is insufficient, acupuncture appears to be beneficial to increase the clinical pregnancy rate in women undergoing IVF-ET. However, there are severe heterogeneity and methodological quality defects, which limit the reliability of results. Further, high-quality primary studies are still needed.

Main characteristics of IVF / ICSI protocols in patients with suboptimal response to controlled ovarian stimulation

Hypothesis/Aims of study: According to the number of oocytes retrieved in IVF/ICSI protocols, the ovarian response to controlled ovarian stimulation is divided into: poor (03 oocytes), suboptimal (49 oocytes), normal (1015 oocytes) and excessive (15 oocytes) response. However, the effectiveness of IVF / ICSI programs in women with a suboptimal response is poorly understood, since this cohort of patients is often fallen into the category of women with a normal response. The aim of this study was to determine the main characteristics of IVF / ICSI programs in patients with suboptimal response to be further compared to those in women with normal response to controlled ovarian stimulation.&#x0D; Study design, materials and methods: This retrospective study included 568 patients: 470 women with suboptimal response and 98 women with normal response to controlled ovarian stimulation. The comparative analysis comprised clinical and anamnestic data, as well as the main characteristics of assisted reproductive technology programs in the selected clinical groups.&#x0D; Results: It was found that patients with suboptimal response to controlled ovarian stimulation had significantly more frequent history of pelvic surgery (71.3 % vs. 55.1 %; p 0.01) and pelvic inflammatory diseases (70.9% vs. 60.2%; p 0.05). Parameters of ovarian reserve (serum anti-Mllerian hormone level and antral follicle count) in women with suboptimal response were significantly lower (p 0.001). In addition, the number of mature oocytes, 2PN zygotes, good quality embryos (p 0.001), as well as the clinical pregnancy rate in women with suboptimal response were found to be significantly lower than in patients with normal response to controlled ovarian stimulation (27.2% vs. 41.7%; p 0.01). It was noted that concomitant uterine fibroids enhanced the negative impact on the effectiveness of IVF / ICSI programs in women with suboptimal response to controlled ovarian stimulation (OR = 0.5; 95% CI: 0.30.9; p = 0.03). ROC analysis identified predictors of suboptimal response to controlled ovarian stimulation, such as serum anti-Mllerian hormone level (AUC = 0.80) with the cut-off value of 2.57 ng / ml (sensitivity 74%, specificity 75%) and antral follicle count (AUC = 0.90) with the cut-off value of 10 follicles (sensitivity 80%, specificity 94%).&#x0D; Conclusion: In women with suboptimal response to controlled ovarian stimulation, IVF / ICSI success rates are significantly reduced when compared to those in women with normal response. Concomitant uterine fibroids may further decrease the effectiveness of IVF / ICSI protocols in patients with suboptimal response. Predictors of suboptimal response include the serum anti-Mllerian hormone level and antral follicle count.

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)).

Failure of implantation and conception may result from inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation. To determine effects of assisted hatching (AH) of embryos derived from assisted conception on live birth and multiple pregnancy rates. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register (until May 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; until May 2020), in the Cochrane Library; MEDLINE (1966 to May 2020); and Embase (1980 to May 2020). We also searched trial registers for ongoing and registered trials (http://www.clinicaltrials.gov - a service of the US National Institutes of Health; http://www.who.int/trialsearch/Default.aspx - The World Health Organization International Trials Registry Platform search portal) (May 2020). Two review authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical, or laser disruption of the zona pellucida before embryo replacement) versus no AH that reported live birth or clinical pregnancy data. We used standard methodological procedures recommended by Cochrane. Two review authors independently performed quality assessments and data extraction. We included 39 RCTs (7249 women). All reported clinical pregnancy data, including 2486 clinical pregnancies. Only 14 studies reported live birth data, with 834 live birth events. The quality of evidence ranged from very low to low. The main limitations were serious risk of bias associated with poor reporting of study methods, inconsistency, imprecision, and publication bias. Five trials are currently ongoing. We are uncertain whether assisted hatching improved live birth rates compared to no assisted hatching (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.92 to 1.29; 14 RCTs, N = 2849; I² = 20%; low-quality evidence). This analysis suggests that if the live birth rate in women not using assisted hatching is about 28%, the rate in those using assisted hatching will be between 27% and 34%. Analysis of multiple pregnancy rates per woman showed that in women who were randomised to AH compared with women randomised to no AH, there may have been a slight increase in multiple pregnancy rates (OR 1.38, 95% CI 1.13 to 1.68; 18 RCTs, N = 4308; I² = 48%; low-quality evidence). This suggests that if the multiple pregnancy rate in women not using assisted hatching is about 9%, the rate in those using assisted hatching will be between 10% and 14%. When all of the included studies (39) are pooled, the clinical pregnancy rate in women who underwent AH may improve slightly in comparison to no AH (OR 1.20, 95% CI 1.09 to 1.33; 39 RCTs, N = 7249; I² = 55%; low-quality evidence). However, when a random-effects model is used due to high heterogeneity, there may be little to no difference in clinical pregnancy rate (P = 0.04). All 14 RCTs that reported live birth rates also reported clinical pregnancy rates, and analysis of these studies illustrates that AH may make little to no difference in clinical pregnancy rates when compared to no AH (OR 1.07, 95% CI 0.92 to 1.25; 14 RCTs, N = 2848; I² = 45%). We are uncertain about whether AH affects miscarriage rates due to the quality of the evidence (OR 1.13, 95% CI 0.82 to 1.56; 17 RCTs, N = 2810; I² = 0%; very low-quality evidence). This update suggests that we are uncertain of the effects of assisted hatching (AH) on live birth rates. AH may lead to increased risk of multiple pregnancy. The risks of complications associated with multiple pregnancy may be increased without evidence to demonstrate an increase in live birth rate, warranting careful consideration of the routine use of AH for couples undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). AH may offer a slightly increased chance of achieving a clinical pregnancy, but data quality was of low grade. We are uncertain about whether AH influences miscarriage rates.

Suboptimal response to controlled ovarian stimulation in IVF / ICSI cycles

Hypothesis/Aims of study. Currently, the frequency of suboptimal response (4-9 retrieved oocytes) to controlled ovarian stimulation (COS) in woman is quite high; however, its efficacy is poorly studied. The aim of this study was to evaluate the main characteristics of IVF / ICSI programs in patients with a suboptimal response to COS.&#x0D; Study design, materials and methods. We performed a retrospective study of 412 IVF / ICSI cycles in women with a suboptimal response to COS, including a comparative analysis of clinical and embryological parameters, ovarian reserve and the efficacy of IVF / ICSI protocols.&#x0D; Results. Clinical pregnancy rate in ovarian stimulation cycles with a suboptimal response to COS was 27.9%. The efficacy of assisted reproductive technology (ART) programs in women with uterine fibroids was significantly lower than in patients without fibroids (19.1% vs. 30.5%, p = 0.03; OR = 0.54; 95% CI: 0.31-0.95). Clinical pregnancy rate in patients with male factor infertility was significantly higher than in women with anovulation (37.1% vs. 20.9%, р = 0.005; OR = 2.24; 95% CI: 1.27-3.94) or tubal factor infertility (37.1% vs. 24.8%, р = 0.02; OR = 1.79; 95% CI: 1.09-2.94). There were significant correlations between the number of retrieved oocytes with serum anti-Mllerian hormone (AMH) concentration (r = 0.32, p 0.001) and antral follicle count (AFC) (r = 0.38, p 0.001). In addition, the need for follicle-stimulating hormone (FSH) preparations during COS correlated significantly with ovarian reserve parameters (AMH and AFC) (r = 0.45 and 0.44, both p 0.001, respectively) and the age of patients (r = 0.47; p 0.001).&#x0D; Conclusion. The clinical pregnancy rate in women with a suboptimal response to COS was low. Concomitant uterine fibroids represented an additional factor of negative influence on IVF / ICSI outcomes in women with a suboptimal response to COS. The male factor of infertility in patients with a suboptimal response did not reduce the efficacy of ART programs. Ovarian reserve parameters in women with a suboptimal response correlated with the need for FSH preparations during COS and the number of retrieved oocytes.

Evaluating the Contribution of Oocyte, Sperm, and Uterus in Determining the Outcome of Intracytoplasmic Sperm Injection - A Retrospective Observational Comparative Study on Intracytoplasmic Sperm Injection using Own Oocytes and Donor Oocytes.

Context:Several studies have assessed the contribution of oocyte, sperm, and endometrium on the outcome of intracytoplasmic sperm injection (ICSI) separately. This study assesses the relative contribution of oocyte, sperm, and uterus in achieving clinical pregnancy (CP) through ICSI by comparing own and third-party ICSI cycles.Aim:The aim of the study is to evaluate and compare the strength of contribution of oocyte, sperm, and uterus in achieving CP through ICSI.Settings and Design:This retrospective observational study of ICSI cycles for 20 months including 1000 embryo transfers (ETs).Methodology:Subjects were divided into two groups, Group 1 – ICSI with own oocytes (550 ETs) and Group 2 – ICSI with donor oocytes (450 ETs). Both the groups had 3 subgroups – a (husband sperm, transferred to self), b (donor sperm, transferred to self), c (husband sperm, transferred to a gestational surrogate). CP rate (CPR) as a major outcome was studied in the groups and subgroups.Statistical Analysis:CPR was compared between various subgroups using Z-test and Chi-square of significance of difference between proportions. A P < 0.05 was taken as the level of statistical significance.Results:CPR in subgroup 1a < 35 years, 1a ≥35 years, and 2a was 42.98%, 26.21%, and 40.92%, respectively (P = 0.001). CPR was compared between 2a and 2c (40.92%, 56.5%, P = 0.044) and between 2a and 2b (40.92%, 42.11%, P = 0.866). Implantation rate was highest in Group 2c (34.88%) compared to other subgroups.Conclusion:The higher CPR in women <35 years undergoing ICSI with own oocytes than older women and a comparable CPR as that of recipients of donor oocytes suggests that age thereby oocyte quality is the strongest determining factor in achieving clinical pregnancy. Among oocyte recipients, higher CPR in surrogate uterus than patient uterus suggests that uterus/endometrium plays a considerable role, and comparable CPR between ICSI using husband sperm and donor sperm indicates that sperm quality might not play a major role in achieving CP.

Effect of Body Mass Index on the Outcome of In-vitro Fertilization/Intracytoplasmic Sperm Injection

&lt;p&gt;Background and Objective: &amp;nbsp;Obesity is becoming a global issue related to many health problems, and infertility is one of them. It has been established in literature that obesity or increased body mass index (BMI) harms the ability of a woman to conceive. Assisted reproductive techniques e.g., in-vitro fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) are helping infertile women to conceive. This study's objective was to analyze the effect of BMI on IVF/ICSI treatment outcomes in infertile women.&lt;/p&gt;&#x0D; &lt;p&gt;Methods: &amp;nbsp;This was a retrospective cross-sectional study. Samples of 500 patients aged less than 40 years were selected at a tertiary care infertility center: Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital. The sample was collected from January 2019 to June 2019. A structured proforma was used to collect information about selected anthropometric measurements and ultrasonography findings from the files and follow-ups of the selected patients. Data was processed and analyzed in Statistical Package for Social Sciences (SPSS) version 20.0.&lt;/p&gt;&#x0D; &lt;p&gt;Results: &amp;nbsp;The age of the subjects ranged from 18 to 39 years, with a maximum number of subjects in the age category 31 to 35 years. BMI was significantly associated with number of follicles retrieved and clinical pregnancy rate (P= &amp;nbsp;0.001).&lt;/p&gt;&#x0D; &lt;p&gt;Conclusion: &amp;nbsp;Normal BMI has positive impact both on follicular response in controlled ovarian stimulation (COS) and clinical pregnancy rates in women undergoing IVF/ICSI treatment.&lt;/p&gt;

Effect of Body Mass Index on the Outcome of In-vitro Fertilization/Intracytoplasmic Sperm Injection

Background and Objective: Obesity is becoming a global issue related to many health problems, and infertility is one of them. It has been established in literature that obesity or increased body mass index (BMI) harms the ability of a woman to conceive. Assisted reproductive techniques e.g., in-vitro fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) are helping infertile women to conceive. This study's objective was to analyze the effect of BMI on IVF/ICSI treatment outcomes in infertile women. Methods: This was a retrospective cross-sectional study. Samples of 500 patients aged less than 40 years were selected at a tertiary care infertility center: Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital. The sample was collected from January 2019 to June 2019. A structured proforma was used to collect information about selected anthropometric measurements and ultrasonography findings from the files and follow-ups of the selected patients. Data was processed and analyzed in Statistical Package for Social Sciences (SPSS) version 20.0. Results: The age of the subjects ranged from 18 to 39 years, with a maximum number of subjects in the age category 31 to 35 years. BMI was significantly associated with number of follicles retrieved and clinical pregnancy rate (P= 0.001). Conclusion: Normal BMI has positive impact both on follicular response in controlled ovarian stimulation (COS) and clinical pregnancy rates in women undergoing IVF/ICSI treatment.

The impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer

BackgroundThe aim of this study was to investigate the impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer.MethodsBlood samples were collected on the first visit to our department and 14 days after embryo transfer. Women were divided into three groups based on D14 TSH levels, which were compared to basal TSH levels in groups with different clinical outcomes. TSH levels between pregnant and nonpregnant women were also compared.ResultsThe clinical pregnancy rate in women with lower TSH levels 14 days after transfer was slightly but significantly lower (56%, P = 0.05) compared to those with higher TSH levels. Furthermore, TSH levels were significantly elevated 14 days after transfer compared to basal TSH levels in pregnant women and in women who successfully became pregnant (P < 0.001, respectively).ConclusionsElevated TSH levels 14 days after embryo transfer compared to basal TSH levels seem to play a protective role and predict favorable clinical outcomes under specific conditions.

Impact of vitamin D on human embryo implantation—a prospective cohort study in women undergoing fresh embryo transfer

To measure free and total 25-hydroxyvitamin D [25(OH)D] immediately before embryo transfer and analyze its association with early pregnancy outcome parameters such as biochemical pregnancy, implantation rate, and clinical pregnancy rates in women undergoing fresh embryo transfer after their first ovarian hyperstimulation. Prospective cohort study. Academically affiliated private fertility center. A total of 2,569 women undergoing fresh embryo transfer after ovarian hyperstimulation. None. The study end points were biochemical pregnancy rate, implantation rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriages, and ongoing pregnancy rate. Free and total 25(OH)D concentrations were measured 1 day before embryo transfer. Total 25(OH)D correlated with free 25(OH)D. Total and free 25(OH)D serum concentrations were similar in those patients reaching and not reaching the study outcomes (biochemical pregnancy rate, implantation rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriages, and ongoing pregnancy rate). There was likewise no statistical difference when analyzing the frequency of all study outcomes in quintiles of either total or free 25(OH)D. In addition, the study population was divided into three groups according to the total vitamin D status based on clinical practice guideline. All outcomes were similar in women with adequate, insufficient, and deficient total 25(OH)D. Multiple linear regression analysis considering confounding likewise indicated no association of free or total vitamin D with any of the study outcomes. Neither free nor total 25(OH)D concentration at embryo transfer was associated with successful embryo implantation in women undergoing fresh transfer after ovarian hyperstimulation.