Premature Progesterone Rise Is Associated with Higher Cumulative Live Birth Rate with Freeze-All Strategy.

Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups based on serum progesterone levels at the time of hCG administration: 526 cycles had levels below 1.5 ng/mL, while 149 cycles had levels equal to or above 1.5 ng/mL. Results: The findings revealed a significantly higher number of mature follicles and retrieved oocytes in patients with PPR across all AMH categories. Multiple analyses revealed factors influencing PPR, including the duration of induction and the number of retrieved oocytes. Within the same oocyte retrieval number group, patients with PPR demonstrated non-inferior pregnancy outcomes compared to non-PPR patients. Upon adjustment for age, AMH, and total follicle-stimulating hormone (FSH) dosage, PPR maintained a positive correlation with the cumulative live birth rate (LBR). Conclusions: The study showed that PPR correlates with an increase in retrieved oocytes while maintaining similar embryo quality and oocyte retrieval rates and results in a higher cumulative LBR.

A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Dinoprostone tablet versus continuous vaginal insert (Propess®) for elective induction in low-risk nulliparous women at term.

OBJECTIVE: To evaluate the efficacy and safety of dinoprostone tablet and continuous vaginal insert (Propess®) in low-risk nulliparous women at term with insufficient cervical ripening receiving elective induction. MATERIALS AND METHODS: A retrospective study was conducted between March 2020 and February 2022 and included 230 women who underwent elective induction with dinoprostone tablet or vaginal insert. The primary endpoint was failure of induction. Secondary endpoints included time to vaginal delivery, vaginal delivery rate, as well as maternal and neonatal complications and adverse outcomes. RESULTS: No statistically significant differences were found between the two groups regarding the main outcome measures; however, the high responders had a significant higher proportion of hyperstimulation and non-reassuring fetal status. The high responder in the Propess group was statistically significant younger (31.68 ± 4.73 vs. 33.82 ± 4.39, p = 0.027), while they had a significantly lower BMI at delivery time of the tablet group (24.49 ± 2.24 vs. 27.42 ± 4.32, p = 0.024). Factors associated with success of vaginal delivery within 24 h (p = 0.015, OR = 0.9, 95%CI = 0.82-0.98) and the Cesarean section (p < 0.001, OR = 1.17, 95%CI = 1.08-1.27) was BMI at delivery time. CONCLUSION: Slow-release vaginal insert and dinoprostone tablet had similar efficacy and safety for elective induction in low risk nulliparous women at term. Women with younger maternal age or lower BMI at delivery time may have a better response to dinoprostone and had a significantly higher proportion of hyperstimulation and non-reassuring fetal status.

Impact of adenomyosis and endometriosis on IVF/ICSI pregnancy outcome in patients undergoing gonadotropin-releasing hormone agonist treatment and frozen embryo transfer.

Although numerous studies have attempted to establish the relationship between adenomyosis and infertility, no consensus has emerged. Our aim was to investigate whether adenomyosis and endometriosis affected IVF outcomes in our patients. This was a retrospective study of 1720 patients from January 2016 to December 2019. In total, 1389 cycles were included: 229 cycles in the endometriosis group (group E), 89 cycles in the adenomyosis group (group A), 69 cycles in the endometriosis and adenomyosis group (group EA), and 1002 cycles in the control group (group C). Most patients in groups A and EA received GnRH agonist treatment before FET. The 1st FET live birth rates (LBR) were 39.3%, 32.1%, 25% and 48.1% in groups E, A, EA, and C. The miscarriage rates were 19.9%, 34.7%, 39%, and 17.6%. The per retrieval cycle cumulative live birth rates (cLBRs) in patients < 38 y/o were 56.4%, 58.1%, 44.8%, and 63%. The per retrieval cycle cLBRs in patients ≥ 38 y/o were 25%, 9.8%, 17.2%, and 29.5%. Among groups A and EA, LBRs were 25.58% and 18.89% in patients with a ≥ sevenfold decrease and a < sevenfold decrease in CA-125 level, respectively, after GnRH agonist treatment. Endometriosis was not associated with a poorer pregnancy outcome. Patients with adenomyosis with/without endometriosis had higher miscarriage rates, lower LBRs, and lower cLBRs, especially in patients aged ≥ 38 years, even after GnRH agonist treatment before FET cycles. Patients who have a greater than sevenfold decrease in CA-125 level after GnRH agonist treatment might have better clinical pregnancy outcomes.

Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.

PURPOSE: This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis. METHODS: A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma. Patients were further divided into primary endometrioma, recurrent endometrioma and those having received cystectomy for endometrioma prior to IVF/ICSI. The control group included 624 infertile women without endometriosis. RESULTS: In the endometrioma subgroup (B) the blastocyst formation rate was significantly lower when compared with the endometriosis (A) and control groups (C). The cumulative live birth rates (CLBRs) (60.5% versus 49.4% versus 56.9%, p = 0.194 in A versus B, p = 0.406 in A versus C, p = 0.878 in B versus C) were comparable. Multiple logistic regression analysis revealed that female age, total FSH dose and blastocyst formation rate were the significant variables in predicting CLBR (OR 0.89, CI 0.80-0.99, p < 0.025, OR 0.68 CI 0.53-0.88, p = 0.003 and OR 30.04, CI 9.93-90.9, p < 0.001, respectively). The CLBRs were comparable at 47.1%, 60% and 57.9% in the primary endometrioma, s/p cystectomy and recurrent endometrioma group. CONCLUSION: Although the blastocyst formation rate was lower in the endometrioma group, CLBR was not worse than those who were in the endometriosis or control group. Cystectomy for endometrioma did not alter IVF/ICSI outcomes if the ovarian reserve was comparable. Recurrent endometrioma did not worsen IVF/ICSI outcomes than primary endometrioma.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

Corrigendum: A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

[This corrects the article DOI: 10.3389/fendo.2022.931756.].

A retrospective, matched case-control study of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

Background: The role of luteinizing hormone (LH) in controlled ovarian hyperstimulation (COH) requires more evidence for its efficacy. Several studies compared recombinant human LH (r-hLH) or human menopausal gonadotropin (hMG) in combination with recombinant human follicle-stimulating hormone (r-hFSH) but lack the results with GnRH-antagonist protocol and in Asians. Methods: This is a retrospective, single-center study inspecting women receiving GnRH antagonist protocol and r-hFSH+hMG or r-hFSH+r-hLH regimen for over five days for COH in the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in Taiwan from 2013 to 2018. The outcomes of IVF/ICSI cycles were analyzed after propensity score matching between the two groups. A subgroup analysis was conducted in cycles in which women underwent their first embryo transfer (ET), including fresh ET and frozen ET (FET). Results: With a total of 503 cycles, the results revealed that the r-hFSH+r-hLH group performed better in terms of numbers of oocytes retrieved (r-hFSH+hMG vs. r-hFSH+r-hLH, 11.7 vs. 13.7, p=0.014), mature oocytes (8.7 vs. 10.9, p=0.001), and fertilized oocytes (8.3 vs. 9.8, p=0.022), while other outcomes were comparable. The analysis of first ET cycles also showed similar trends. Although the implantation rate (39% vs. 43%, p=0.37), pregnancy rate (52% vs. 53%, p=0.90), and live birth rate (39% vs. 45%, p=0.19) were not significantly different, the miscarriage rate was higher in the r-hFSH+hMG group than the r-hFSH+r-hLH group (26% vs. 15%, p<0.05) in first ET cycles. The cumulative pregnancy rate was significantly higher in the r-hFSH+r-hLH group (53% vs. 64%, p=0.02). No significant difference in rates of ovarian hyperstimulation syndrome (OHSS) was observed. Conclusion: The results support the hypothesis that the treatment of r-hLH+r-hFSH improves COH clinical outcomes in the IVF/ICSI cycle.

Contamination of ART culture Media-The role of semen and strategies for prevention.

OBJECTIVE: Microbial contamination of ART culture media is rare but serious. We examined our own experience and conducted a review of the literature with a view to preventing its occurrence and recurrence. CASE REPORT: A total of 12 cases were recorded during January 2006 to March 2019. The contaminations were caused by semen and were shown to be bacteria that were resistant to the prophylactic antibiotics used in the medium. After the procedures were cancelled due to contaminations, nine husbands received antibiotic treatment, while nine couples changed over to the ICSI program. Eventually, eight couples concluded the study with live birth deliveries, and there was no recurrence of contamination. CONCLUSION: ART laboratories should preserve all sperm suspension samples until embryo transfer has been completed for the purpose of checking whether contamination has occurred. In addition to antibiotic treatment, implementation of the ICSI procedure during the next ART cycle has already been proven to be effective. In the future, the zona-removal technique may be considered as another potential option.

Cost-effectiveness of freeze-all policy - A retrospective study based upon the outcome of cumulative live births.

OBJECT: We have previously reported that cumulative live birth rates (CLBRs) are higher in the freeze-all group compared with controls (64.3% vs. 45.8%, p = 0.001). Here, we aim to determine if the freeze-all policy is more cost-effective than fresh embryo transfer followed by frozen-thawed embryo transfer (FET). MATERIALS AND METHODS: The analysis consisted of 704 ART (Assisted reproductive technology) cycles, which included in IVF (In vitro fertilisation) and ICSI (Intra Cytoplasmic Sperm Injection) cycles performed in Taichung Veterans General Hospital, Taiwan between January 2012 and June 2014. The freeze-all group involved 84 patients and the fresh Group 625 patients. Patients were followed up until all embryos obtained from a single controlled ovarian hyper-stimulation cycle were used up, or a live birth had been achieved. The total cost related to treatment of each patient was recorded. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-all strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed. RESULTS: The total treatment cost per patient was significantly higher for the freeze-all group than in the fresh group (USD 3419.93 ± 638.13 vs. $2920.59 ± 711.08 p < 0.001). However, the total treatment cost per live birth in the freeze-all group was US $5319.89, vs. US $6382.42 in the fresh group. CEAC show that the freeze-all policy was a cost-effective treatment at a threshold of US $2703.57 for one additional live birth. Considering the Willingness-to-pay threshold per live birth, the probability was 60.1% at the threshold of US $2896.5, with the freeze-all group being more cost-effective than the fresh-ET group; or 90.1% at the threshold of $4183.8. CONCLUSION: The freeze-all policy is a cost-effective treatment, as long as the additional cost of US $2703.57 per additional live birth is financially acceptable for the subjects.

Does the "freeze-all" policy allow for a better outcome in assisted reproductive techniques than the use of fresh embryo transfers? - A retrospective study on cumulative live birth rates.

OBJECTIVE: There are increasing concerns regarding the adverse effects associated with control ovarian hyperstimulation (COH) in both endometrial and uterine environments. With the "segmentation treatment policy" of assisted reproductive techniques (ART), endometrial problems may be obviated through embryo cryopreservation. However, it remains unclear if the "freeze-all policy" offers a better outcome when compared with fresh embryo transfer (ET). To clarify this, we compared the cumulative live birth rates (CLBRs) between these two patient populations. MATERIALS AND METHODS: This is a retrospective study on 853 patients undergoing ovarian stimulation and ART (including IVF/ICSI) during the period from January 2012 to June 2014 in Taichung Veterans General Hospital, Taiwan, ROC. We followed up with these patients through to November 2016. Patients whose embryos were not completely transferred back were excluded. The study group ('freeze-all') included 84 patients whose cycles were performed initially without fresh ET, but were later given frozen-thawed ET. The control group ('fresh ET') had 625 patients whose cycles were performed with fresh ET, followed by frozen-thawed ET. Basic parameters and CLBRs were statistically compared between these two groups. RESULTS: The CLBRs in the study group were significantly higher than those in the control group (64.3% vs. 45.8%, p = 0.001). Subgroup analysis revealed that when the number of oocyte pick up (OPU) is between 4 and 15, the CLBRs in the study group were significantly better (58.3% vs. 40.9%, p = 0.042). For those with OPU <4 or OPU >15 the CLBRs were similar in these two groups (OPU < 4: study vs. control 23.1% vs. 18.8% respectively, p = 0.713; OPU>15: study vs. control 85.7% vs. 80.8% respectively, p = 0.625) CONCLUSION: The Freeze-all policy improved the ART outcome for normal responders.

Maternal outcome after conservative management of abnormally invasive placenta.

OBJECTIVE: The purpose of this study was to describe our preliminary experience of the efficacy and safety of a conservative strategy for abnormally invasive placenta. MATERIALS AND METHODS: A retrospective review of eight pregnant women with abnormally invasive placenta (one with placenta previa accrete, three with placenta previa increta, and four with previa percreta) was performed. The diagnosis was made by prenatal ultrasonography, and was confirmed by operative and histopathological findings. Patients who desired future fertility or who had extensive diseases were selected as candidates after panel meeting. Conservative management after obtaining informed consent was defined by a primary cesarean delivery before 35 weeks of gestation with the abnormally adherent placenta left in situ, partially or totally. The primary outcome was successful uterine preservation. The secondary outcome was severe maternal morbidity including sepsis, coagulopathy, immediate or delayed hemorrhage bladder injury, and fistula. RESULTS: Among the eight patients, the mean age was 34 ± 3 years (range, 30-40 years). All women had risk factors, such as placental previa, previous cesarean delivery and/or dilation & curettage, for abnormally invasive placenta. Seven women underwent planned cesarean delivery at the mean gestation age of 34 weeks (range, 31-37 weeks). One woman received hysterotomy at 18 weeks. In our series, the uterus was preserved in only two cases (25%), one who received hysterotomy at a relatively young gestational age and another who had mild disease. Mean maternal blood loss during primary cesarean delivery was 528 ± 499 ml (range, 100 ml-1,500 ml). Severe maternal morbidity was recorded in seven out of eight patients (87.5%). CONCLUSION: In this small series, we observed a low successful uterine preservation rate and a high maternal complication rate. We recommend that primary cesarean hysterectomy should be used as the treatment of choice for mild to severe abnormally invasive placenta. Conservative management should be reserved for women with a strong fertility desire and women with extensive disease that precludes primary hysterectomy due to surgical difficulty.

Temporary prophylactic intravascular balloon occlusion of the common iliac arteries before cesarean hysterectomy for controlling operative blood loss in abnormal placentation.

OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of temporary prophylactic intravascular balloon occlusion of the common iliac arteries (CIA) before planned cesarean hysterectomy for controlling operative blood loss in abnormal placentation. MATERIALS AND METHODS: A retrospective study of 13 pregnant women at risk for placenta accreta identified using sequential obstetric ultrasonography and magnetic resonance imaging from January 2007 to December 2009 was performed. Temporary prophylactic intravascular balloon catheterization of the bilateral CIA before cesarean hysterectomy was performed by interventional radiologists. The maximum duration of occlusion time of CIA must not exceed 60 minutes. The primary outcome for this study included estimated blood loss and secondary outcomes included the development of thromboembolism, disseminated intravascular coagulation and surgical complications. RESULTS: Among these 13 patients, the mean age of the patients was 32.8 ± 0.7 years (range 29-37 years). The mean gestational age at cesarean hysterectomy was 32.2 ± 0.9 weeks (range 28-36 weeks), and the mean intraoperative blood loss was 1902.3 ± 578.8 mL (range 500-8000 mL). Operative bleeding was controlled by conservative treatment without additional surgery in two cases. Importantly, two patients (15.8%) had severe complications possibly related to the interventional procedure. One patient was noted to have a popliteal artery thrombosis. A second patient had an external iliac artery thrombosis with 80-90% occlusion. Both patients required antithrombotic treatment without sequelae. CONCLUSION: With limited experience in this small series, we observed a statistically significant reduction in operative blood loss after the use of temporary prophylactic balloon occlusion of the CIA technique compared with historical controls of similar demographic characteristics previously published (1902.3 ± 578.8 mL, range 500-8000 mL vs. 4445.7 ± 996.48 mL, range 1040-15,000 mL, p = 0.0402). Additionally, two patients had arterial thrombosis. These preliminary findings are based on a small number of patients, and therefore further investigation is needed to determine the effectiveness and safety of this new technique.

Luteal phase support with decapeptyl improves pregnancy outcomes in intracytoplasmic sperm injection with higher basal follicle-stimulating hormone or lower mature oocytes.

BACKGROUND: The role of midluteal phase gonadotropin-releasing hormone (GnRH) agonist had been an issue of debate. The aim of this retrospective study was to evaluate the effect of a mid-luteal phase GnRH agonist as an additional luteal phase support (LPS) in patients receiving intracytoplasmic sperm injection (ICSI). Additionally, we elucidate which subgroup would gain the most benefit from GnRH agonist as LPS. METHODS: The medical records were retrieved from January 2009 to January 2012 and a total of 348 patients receiving ICSI were included in this retrospective study. Among them, 240 patients met the inclusion criteria of patients aged ≤ 38 years, previous assisted reproductive technology (ART) cycles ≤ 2. There were 147 patients in the decapeptyl group who received GnRH agonist decapeptyl 6 days after ICSI as additional LPS and 93 patients in the control group. Subgroupings were done according to advanced age, the number of previous ART cycles, high basal follicle-stimulating hormone (FSH) level, and patients who had fewer mature oocytes retrieved. Live birth rates, clinical pregnancy rate (CPR), and implantation rate were the primary outcomes. RESULTS: LPS with decapeptyl led to a higher implantation rate (24.5% vs. 17.0%, p = 0.023), a higher CPR (49.0%, n = 72 vs. 33.3%, n = 31, p = 0.023) and a higher live birth rate (41.5%, n = 61 vs. 28.0%, n = 26, p = 0.039). In the subgroup analysis, decapeptyl improved the CPR of those patients with basal FSH >8 mIU/mL (50.0%, n = 15 vs. 8.3%, n = 1, p = 0.031) and also improved CPR (42.3%, n = 11 vs. 0%, n = 0, p = 0.017) and live birth rate (30.8%, n = 8 vs. 0%, n = 0, p = 0.035) of patients whose number of mature oocytes was three or fewer. CONCLUSION: This study demonstrated that administration of decapeptyl as additional luteal support can enhance ICSI clinical outcomes. Those patients with higher basal FSH level or fewer number of mature oocytes may obtain particularly significant benefit.

Extensive hepatic infarction in severe preeclampsia as part of the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): evolution of CT findings and successful treatment with plasma exchange therapy.

OBJECTIVE: We describe the serial computed tomography (CT) findings of extensive hepatic infarction and successful plasma exchange therapy in a severe preeclamptic woman with postpartum HELLP syndrome. CASE REPORT: A 38 year-old woman presented with elevated blood pressure of 140-180/90-120 mmHg and 3+ proteinuria at 28 weeks of gestation. Two days after admission, the patient suddenly complained of severe epigastric pain and headache. Her blood pressure rose sharply to 195/120 mmHg. A 980 g female was delivered by emergency cesarean section. Following delivery, the patient's clinical condition and laboratory values deteriorated, with progressive liver insufficiency (peak AST level = 4246 IU/L, ALT = 3685 IU/L, LDH = 6237 IU/L, platelets = 72,000/mm(3)). Two consecutive plasma exchanges (PEX) were undertaken on the 3(rd) and 4(th) postpartum day. A contrast-enhanced CT of the abdomen performed 8 days postpartum showed geographically wedge-shaped areas of low attenuation, with a mottled appearance in the right hepatic lobe. Shortly thereafter, the patient recovered and all laboratory parameters gradually normalized 3 weeks after delivery. Follow-up CT-scan of the liver 2 months postpartum showed no evidence of infarction, with complete recovery. CONCLUSION: We recommend that severely ill patients with HELLP syndrome having epigastric pain should undergo CT imaging of the liver. A trial of postpartum PEX therapy should be considered for treatment of the HELLP syndrome complicated with hepatic infarction, which is recalcitrant to conventional medical management, and fails to abate within 72-96 hours of delivery.