Perinatal outcomes of pregnancies following autologous cryopreserved ovarian tissue transplantation: a systematic review with pooled analysis.

OBJECTIVE: This study aimed to synthesize the existing evidence on perinatal outcomes after autologous cryopreserved ovarian tissue transplantation, concurrently identifying key factors influencing these outcomes. DATA SOURCES: A comprehensive search was performed on MEDLINE, Embase, and Cochrane Library databases to identify relevant studies on the effect of autologous cryopreserved ovarian tissue transplantation on perinatal outcomes from inception to October 22, 2023. Where there was missing information, the authors were contacted for updated data. STUDY ELIGIBILITY CRITERIA: Observational studies, such as cohort studies, case series, and case reports that reported a live birth after autologous cryopreserved ovarian tissue transplantation, were considered eligible. Studies lacking data on women's demographic characteristics, autologous cryopreserved ovarian tissue transplantation procedure details, or perinatal outcomes were excluded. In addition, cases involving fresh or nonautologous transplantations and those addressing primary ovarian insufficiency were excluded. METHODS: Two reviewers (M.E. and E.U.) independently performed the study selection, data extraction, and risk of bias assessment, and the results were then reviewed together. The PRISMA guidelines were followed, and the protocol was registered on PROSPERO (CRD42023469296). RESULTS: This review included 58 studies composed of 122 women with 162 deliveries (154 singletons and 8 twins) after autologous cryopreserved ovarian tissue transplantation, resulting in 170 newborns. Of note, 83.6% of the women had a malignant disease. Moreover, most of these women (51.0%) were exposed to some form of chemotherapy before ovarian tissue cryopreservation. Of the 162 childbirths, 108 (66.7%) were conceived naturally, and 54 (33.3%) were conceived through assisted reproductive techniques. The birthweight of 88.5% of newborns was appropriate for gestational age, whereas 8.3% and 3.1% were small for gestational age and large for gestational age, respectively. The preterm birth rate was 9.4%, with the remaining being term deliveries. Hypertensive disorders of pregnancy were noted in 18.9% of women, including pregnancy-induced hypertension in 7.6%, preeclampsia in 9.4%, and hemolysis, elevated liver enzymes, and low platelet count in 1.9%. The incidences of gestational diabetes mellitus and preterm premature rupture of membranes were 3.8% for each condition. Neonatal anomalies were reported in 3 transplant recipients with 4 newborns: arthrogryposis, congenital cataract, and diaphragmatic hernia in a twin. Finally, among the recipients' characteristics, not receiving chemotherapy before ovarian tissue cryopreservation (odds ratio, 0.23; 95% confidence interval, 0.07-0.72; P=.012) and natural conception (odds ratio, 0.29; 95% confidence interval, 0.09-0.92; P=.035) were associated with a lower perinatal complication rate. CONCLUSION: On the basis of low certainty evidence from observational studies, perinatal complication rates did not increase after autologous cryopreserved ovarian tissue transplantation compared with the general pregnant population, except for preeclampsia. This could be due to chemotherapy exposure, underlying medical conditions, and the common use of assisted reproductive techniques. Further larger studies are needed to explore the causes of increased preeclampsia incidence in autologous cryopreserved ovarian tissue transplantation pregnancies.

The true natural cycle frozen embryo transfer - impact of patient and follicular phase characteristics on serum progesterone levels one day prior to warmed blastocyst transfer.

BACKGROUND: In a true-natural cycle (t-NC), optimal progesterone (P4) output from the corpus luteum is crucial for establishing and maintaining an intrauterine pregnancy. In a previous retrospective study, low P4 levels (< 10 ng/mL) measured one day before warmed blastocyst transfer in t-NC were associated with significantly lower live-birth rates. In the current study, we aim to examine the relationship between patient, follicular-phase endocrine and ultrasonographic characteristics, and serum P4 levels one day prior to warmed blastocyst transfer in t-NC. METHOD: 178 consecutive women undergoing their first t-NC frozen embryo transfer (FET) between July 2017-August 2022 were included. Following serial ultrasonographic and endocrine monitoring, ovulation was documented by follicular collapse. Luteinized unruptured follicle (LUF) was diagnosed when there was no follicular collapse despite luteinizing-hormone surge (> 17 IU/L) and increased serum P4 (> 1.5 ng/mL). FET was scheduled on follicular collapse + 5 or LH surge + 6 in LUF cycles. Primary outcome was serum P4 on FET - 1. RESULTS: Among the 178 patients, 86% (n = 153) experienced follicular collapse, while 14% (n = 25) had LUF. On FET-1, the median serum luteal P4 level was 12.9 ng/mL (IQR: 9.3-17.2), ranging from 1.8 to 34.4 ng/mL. Linear stepwise regression revealed a negative correlation between body mass index (BMI) and LUF, and a positive correlation between follicular phase peak-E2 and peak-P4 levels with P4 levels on FET-1. The ROC curve analyses to predict < 9.3 ng/mL (< 25th percentile) P4 levels on FET-1 day showed AUC of 0.70 (95%CI 0.61-0.79) for BMI (cut-off: 23.85 kg/m2), 0.71 (95%CI 0.61-0.80) for follicular phase peak-P4 levels (cut-off: 0.87 ng/mL), and 0.68 (95%CI 0.59-0.77) for follicular phase peak-E2 levels (cut-off: 290.5 pg/mL). Combining all four independent parameters yielded an AUC of 0.80 (95%CI 0.72-0.88). The adjusted-odds ratio for having < 9.3 ng/mL P4 levels on FET-1 day for patients with LUF compared to those with follicle collapse was 4.97 (95%CI 1.66-14.94). CONCLUSION: The BMI, LUF, peak-E2, and peak-P4 levels are independent predictors of low serum P4 levels on FET-1 (< 25th percentile; <9.3 ng/ml) in t-NC FET cycles. Recognition of risk factors for low serum P4 on FET-1 may permit a personalized approach for LPS in t-NC FET to maximize reproductive outcomes.

Comparison of the efficacy of subcutaneous versus vaginal progesterone using a rescue protocol in vitrified blastocyst transfer cycles.

RESEARCH QUESTION: Does administration of subcutaneous (s.c.) progesterone support ongoing pregnancy rates (OPR) similar to vaginal progesterone using a rescue protocol in hormone replacement therapy frozen embryo transfer cycles? DESIGN: Retrospective cohort study. Two sequential cohorts - vaginal progesterone gel (December 2019-October 2021; n=474) and s.c. progesterone (November 2021-November 2022; n=249) -were compared. Following oestrogen priming, s.c. progesterone 25 mg twice daily (b.d.) or vaginal progesterone gel 90 mg b.d. was administered. Serum progesterone was measured 1 day prior to warmed blastocyst transfer (i.e. day 5 of progesterone administration). In patients with serum progesterone concentrations <8.75 ng/ml, additional s.c. progesterone (rescue protocol; 25 mg) was provided. RESULTS: In the vaginal progesterone gel group, 15.8% of patients had serum progesterone <8.75 ng/ml and received the rescue protocol, whereas no patients in the s.c. progesterone group received the rescue protocol. OPR, along with positive pregnancy and clinical pregnancy rates, were comparable between the s.c. progesterone group without the rescue protocol and the vaginal progesterone gel group with the rescue protocol. After the rescue protocol, the route of progesterone administration was not a significant predictor of ongoing pregnancy. The impact of different serum progesterone concentrations on reproductive outcomes was evaluated by percentile (<10th, 10-49th, 50-90th and >90th percentiles), taking the >90th percentile as the reference subgroup. In both the vaginal progesterone gel group and the s.c. progesterone group, all serum progesterone percentile subgroups had similar OPR. CONCLUSIONS: Subcutaneous progesterone 25 mg b.d. secures serum progesterone >8.75 ng/ml, whereas additional exogenous progesterone (rescue protocol) was needed in 15.8% of patients who received vaginal progesterone. The s.c. and vaginal progesterone routes, with the rescue protocol if needed, yield comparable OPR.

The effect of ≤6 cm sized noncavity-distorting intramural fibroids on in vitro fertilization outcomes: a systematic review and meta-analysis.

IMPORTANCE: The potential detrimental effects of fibroids on natural fecundity and in vitro fertilization (IVF) outcomes may be influenced by their size, location, and number. The impact of small noncavity-distorting intramural fibroids on reproductive outcomes in IVF is still controversial, with conflicting results. OBJECTIVE(S): To determine whether women with noncavity-distorting intramural fibroids of ≤6 cm size have lower live birth rates (LBRs) in IVF than female age-matched controls with no fibroids. DATA SOURCES: MEDLINE, Embase, Global Health, and Cochrane Library databases were searched from inception until July 1, 2022. STUDY SELECTION AND SYNTHESIS: Women undergoing IVF with noncavity-distorting intramural fibroids ≤6 cm constituted the study group (n = 520), whereas women with no fibroid formed the controls (n = 1392). Female age-matched subgroup analyses were performed to evaluate the impact of different cut-offs for size (≤6, ≤4, and ≤2 cm), location (the International Federation of Gynecology and Obstetrics [FIGO] type-3), and the number of fibroids on reproductive outcomes. Mantel-Haenszel odds ratios (ORs) with 95% confidence intervals (CIs) were used for outcome measures. All statistical analyses were performed using RevMan 5.4.1 MAIN OUTCOME MEASURE(S): The primary outcome measure was LBR. Secondary outcome measures were clinical pregnancy, implantation, and miscarriage rates. RESULT(S): After adopting the eligibility criteria, 5 studies were included in the final analysis. Women with ≤6 cm noncavity-distorting intramural fibroids had significantly lower LBRs (OR: 0.48, 95% CI: 0.36-0.65, 3 studies, I2=0; low-certainty evidence) compared with women with no fibroids. A significant reduction in LBRs was noted in ≤4 cm but not in the ≤2 cm subgroups. The FIGO type-3 fibroids of 2-6 cm size were associated with significantly lower LBRs. Owing to a lack of studies, the impact of the number of noncavity-distorting intramural fibroids (single vs. multiple) on IVF outcomes could not be assessed. CONCLUSION(S): We conclude that 2-6 cm sized noncavity-distorting intramural fibroids have a deleterious effect on LBRs in IVF. The presence of FIGO type-3 fibroids of 2-6 cm size is associated with significantly lower LBRs. Conclusive evidence from high-quality randomized controlled trials, the reference standard study design for studies of health care interventions, is needed before myomectomy might be offered in daily clinical practice to women with such small fibroids before undergoing IVF treatment.

Vitrified-warmed blastocyst transfer timing related to LH surge in true natural cycle and its impact on ongoing pregnancy rates.

RESEARCH QUESTION: Does the timing of warmed blastocyst transfer in true natural cycle (tNC) differ according to six different commonly used definitions of LH surge, and do differences in timing have any impact on ongoing pregnancy rate (OPR)? DESIGN: Prospective monitoring, including repeated blood sampling and ultrasound analyses of 115 warmed blastocyst transfer cycles performed using tNC between January 2017 and October 2021. RESULTS: The reference timing of follicular collapse +5 days would be equivalent to LH surge +6 days in only 5.2-41.2% of the cycles employing the six different definitions of the LH surge. In contrast, the reference timing was equivalent to LH surge +7 days in the majority of cycles (46.1-69.5%) and less commonly to LH surge +8 days (1.8-38.3%) and +9 days (0-10.4%). For each definition of the LH surge, the OPR were comparable among the different warmed blastocyst transfer timings related to the LH surge (LH surge +6/+7/+8/+9 days). When logistic regression analysis was performed to evaluate the independent effect of variation of warmed blastocyst transfer timing (LH surge +6/+7/+8/+9 days) on OPR and taking LH surge +6 days as the reference, change in timing was not an independent predictor of OPR for any of the definitions of the LH surge. CONCLUSIONS: Employing a policy of performing warmed blastocyst transfer on follicular collapse +5 days and using six different definitions of the LH surge, vitrified-warmed embryo transfer timing is indeed equivalent to LH surge +7/+8 and even +9 days in a significant proportion of tNC with comparable reproductive outcomes.

The LH surge and ovulation re-visited: a systematic review and meta-analysis and implications for true natural cycle frozen thawed embryo transfer.

BACKGROUND: Efficient and safe embryo vitrification techniques have contributed to a marked worldwide increase in the use of elective frozen embryo transfer (FET). Pinpointing the day of ovulation, more commonly by documentation of the LH surge and less commonly by ultrasonography, is crucial for timing of FET in a true natural cycle (t-NC) to maximize the reproductive outcome. OBJECTIVE AND RATIONALE: The definition of the onset of the LH surge should be standardized in t-NC FET cycles; however, a clear definition is lacking in the available literature. The first search question concerns the definition of the onset of the LH surge in a natural cycle. The second search question relates to the duration between the onset of the LH surge and ovulation. SEARCH METHODS: We searched PubMed, Web of Science and Cochrane Library databases for two search questions from inception until 31 August 2021. 'Luteinizing hormone'[MeSH] OR 'LH' AND 'surge' terms were used to identify eligible articles to answer the first question, whereas 'Luteinizing hormone'[MeSH] OR 'LH' AND 'surge' OR 'rise' AND 'ovulation'[MeSH] OR 'follicular rupture' OR 'follicular collapse' were the terms used regarding the second question. The included publications were all written in the English language, conducted in women of reproductive age with regular ovulatory cycles and in whom serial serum or urine LH measurement was performed. For the quality and risk of bias assessment of the included studies, the Strengthening the Reporting of Observational Studies in Epidemiology and modified Newcastle Ottawa Scale were used. OUTCOMES: A total of 10 and 8 studies were included for search Questions 1 and 2, respectively. Over the years, through different studies and set-ups, testing in either serum or urine, different definitions for the onset of the LH surge have been developed without a consensus. An increase in LH level varying from 1.8- to 6-fold above the baseline LH level was used in seven studies and an increase of at least two or three standard deviations above the mean of the preceding LH measurements was used in two studies. An LH level exceeding the 30% of the amplitude (peak-baseline LH level) of the LH surge was defined as the onset day by one study. A marked inter-personal variation in the time interval between the onset of the LH surge and ovulation was seen, ranging from 22 to 56 h. When meta-analysis was performed, the mean duration in hours between the onset of the LH surge and ovulation was 33.91 (95% CI = 30.79-37.03: six studies, 187 cycles). WIDER IMPLICATIONS: The definition of the onset of the LH surge should be precisely defined in future well-designed studies employing state-of-art laboratory and ultrasonographic equipment. The window of implantation in a natural cycle is still a black box, and future research is warranted to delineate the optimal interval to time the embryo transfer in t-NC FET cycles. Randomized controlled trials employing different precise endocrine and/or ultrasonographic criteria for timing of FET in a t-NC are urgently required.

Subcutaneous luteal phase progesterone rescue rectifies ongoing pregnancy rates in hormone replacement therapy vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Will luteal phase rescue with additional progesterone increase serum progesterone concentrations and improve reproductive outcomes in patients with low serum progesterone concentrations undergoing hormone replacement therapy (HRT) cycles? DESIGN: Case-control study including 40 consecutive patients with serum progesterone concentrations <8.75 ng/ml on the 5th day of progesterone supplementation who underwent rescue with a daily bolus of 25 mg s.c. progesterone, starting on the afternoon of the 5th day of progesterone administration. For every patient who underwent progesterone rescue, three patients matched by age, body mass index, number of previous attempts and number of blastocysts transferred, with serum progesterone concentration >8.75 ng/ml on the 5th day of progesterone administration served as controls (n = 120). The main outcome measure was ongoing pregnancy rate (OPR). RESULTS: Baseline demographic features and embryological data of the rescue and control groups were comparable. As expected, the mean serum progesterone concentration was lower in the rescue group on the 5th day of progesterone administration (7.84 ± 0.92 versus 15.32 ± 5.02 ng/ml; P < 0.001). Following rescue, the mean serum progesterone concentration on the day of vitrified-warmed embryo transfer (6th day of progesterone administration) was 33.43 ± 10.83 ng/ml (range 14.61-82.64 ng/ml), and the OPR of the rescue and control groups were comparable. CONCLUSIONS: In patients undergoing HRT vitrified-warmed blastocyst transfer with serum progesterone concentrations lower than 8.75 ng/ml 1 day prior to the scheduled embryo transfer (6th day of progesterone administration), additional supplementation with a 25 mg s.c. daily progesterone dose seems to rescue the cycle, resulting in OPR comparable to those of patients with serum progesterone >8.75 ng/ml.

Incremental effects of serum uric acid levels, autonomic dysfunction, and low-grade inflammation on nocturnal blood pressure in untreated hypertensive patients and normotensive individuals.

OBJECTIVES: We aimed to evaluate the associations between nocturnal blood pressure (BP) and serum uric acid (SUA) level, low-grade inflammation, and cardiac autonomic function in untreated dipper and nondipper hypertensive patients and normotensive individuals. STUDY DESIGN: The study included 92 consecutive patients (44 men, 48 women; mean age 51.6 ± 9.7 years) who presented for initial evaluation of hypertension. All patients underwent 24-hour Holter monitoring to assess heart rate variability (HRV) and ambulatory BP. Serum high-sensitivity C-reactive protein (hs-CRP) and SUA levels were measured. Due to the non-normal distribution of hs-CRP and microalbuminuria (MAU), they were normalized by logarithmic transformation. RESULTS: Of the study group, 60 patients (65.2%) were diagnosed as hypertensive (50% nondippers). In univariate correlation analysis, log(MAU) showed a significant correlation with nocturnal BP (r=0.560, p<0.001). Among HRV parameters, SDNN, SDANN, and triangular index were inversely correlated with log(hs-CRP) (r=-0.356, p=0.001; r=-0.350, p=0.001; r=-0.314, p=0.002, respectively) and nighttime BP (r=-0.286, p=0.006; r=-0.251, p=0.02; r=-0.294, p=0.004, respectively). Log(hs-CRP) was positively correlated with nighttime BP (r=0.302, p=0.003). Serum UA levels were correlated with only nocturnal BP; i.e., nocturnal mean (r=0.260, p=0.01), systolic (r=0.249, p=0.016), and diastolic BP (r=0.249, p=0.017). In multiple linear regression analysis, log(hs-CRP) and age were independent predictors of cardiac autonomic dysfunction, and log(hs-CRP), SUA, and HRV parameters were independent predictors of nocturnal BP measurements. CONCLUSION: Our findings suggest the role of low-grade inflammation, uric acid levels, and autonomic dysfunction even in the early stages of hypertension.

The comparison of early and late outcome of direct and conventional stenting of patients with st elevation myocardial infarction.

BACKGROUND: The aim of this study was to compare direct and conventional stenting procedure in the subacute stable phase on short- and long-term results in patients with ST elevation myocardial infarction. METHODS: Eighty-eight clinically stable ST-segment elevation myocardial infarction (STEMI) patients were enrolled into the study. The patients were classified as group I (direct stenting) and group II (conventional stenting - stenting after balloon dilatation). Baseline characteristics of patients were scanned from hospital records. Coronary angiograms before and after the revascularization procedure were evaluated with the quantitative coronary angiogram technique. Patients were followed for 5 years for clinical outcomes. The study population consisted of 58 patients (65%) in group I and 30 patients (35%) in group II. Mean ages were 55.8 +/- 10.8 and 57.3 +/- 9.8, respectively. RESULTS: There were no significant differences between the two groups regarding clinical characteristics (hypertension, diabetes mellitus, family history of cardiovascular disease, smoking and dyslipidemia). The thrombus score was similar in both groups. Diameter stenosis was lower in group I (54.8 +/- 12.7 versus 61.4 +/- 12.6; p = 0.023) and TFC (Thrombolysis in Myocardial Infarction frame count) was higher in group II (30.7 +/- 14.5 versus 40.8 +/- 26.7; p = 0.02) before the percutaneous coronary intervention (PCI). Other quantitative angiographic parameters were not different. For all angiographic criteria, the difference between pre- and post-PCI parameters was significantly different in both groups. However, the change in TFC was higher within the group II compared to pre-PCI TFC rates. This difference was statistically significant (p = 0.002). Procedural success was statistically different between groups (69% in group I, 43% in group II; p50.01). Immediate clinical and angiographic results were similar. At 5-year follow-up the incidence of major adverse cardiac events including death, angina pectoris and myocardial infarction were similar for direct stenting versus conventional angioplasty. CONCLUSIONS: Direct stenting is safe and feasible for the treatment in patients with STEMI at the subacute phase. Immediate clinic, angiographic and late clinical results are similar for direct stenting and conventional stenting following balloon angioplasty. Although conventional stenting improved TFC better than direct stenting, this did not translate to better clinical outcomes.

The optimal time of elective percutaneous coronary intervention for stable patients after ST elevation myocardial infarction.

OBJECTIVE: To find the optimal time (early: < or =3 days; late: >3 days) for revascularization in ST elevation myocardial infarction (STEMI) patients in the subacute phase. METHODS: Ninety-nine STEMI patients who were admitted to Gazi University Faculty of Medicine between 2000 and 2004 were enrolled into this study. Patients were divided into 2 groups according to time from the beginning of symptoms to the percutaneous coronary intervention. Coronary angiograms before and after the revascularization were evaluated using the quantitative coronary angiogram technique. RESULTS: 45 early (group I) and 54 late (group II) revascularized patients were evaluated. There were no significant differences between the 2 groups regarding demographic properties, thrombus score, success of the procedure, quantitative angiographic parameters, and clinical results of the procedure. CONCLUSIONS: Waiting for the development of stable phase in STEMI to apply PCI has no obvious benefit for angiographic and clinical results.

Isolated right ventricular infarction due to occlusion of the right ventricular branch in the absence of percutaneous coronary intervention.

Isolated right ventricular myocardial infarction accounts for only 3% of all infarctions. It has previously been reported as a complication of percutaneous coronary intervention involving the right coronary artery secondary to occlusion of the right ventricular branch. In the present report, a patient is described in whom isolated right ventricular myocardial infarction developed due to occlusion of the right ventricular branch of the right coronary artery in the absence of percutaneous intervention.