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Language: enSubject: IVF

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    Review
    Citation - WoS: 22
    Citation - Scopus: 28
    The Effect of £6 Cm Sized Noncavity-Distorting Intramural Fibroids on in Vitro Fertilization Outcomes: a Systematic Review and Meta-Analysis
    (Elsevier Science inc, 2023) Erden, Murat; Uyanik, Esra; Polat, Mehtap; Ozbek, Irem Yarali; Yarali, Hakan; Mumusoglu, Sezcan
    Importance: The potential detrimental effects of fibroids on natural fecundity and in vitro fertilization (IVF) outcomes may be influ-enced 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 & LE;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 & LE;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 (& LE;6, & LE;4, and & LE;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 5.4.1Main Outcome Measure(s): The primary outcome measure was LBR. Secondary outcome measures were clinical pregnancy, implan-tation, and miscarriage rates.Result(s): After adopting the eligibility criteria, 5 studies were included in the final analysis. Women with & LE;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 & LE;4 cm but not in the & LE;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. (Fertil Sterile 2023;119:996-1007. & COPY;2023 by American Society for Reproductive Medicine.)El resumen esta disponible en Espanol al final del articulo.
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    Article
    Citation - Scopus: 9
    A Drop in Serum Progesterone From Oocyte Pick-Up +3 Days To +5 Days in Fresh Blastocyst Transfer, Using Hcg-Trigger and Standard Luteal Support, Is Associated With Lower Ongoing Pregnancy Rates
    (Oxford University Press, 2023) Uyanik,E.; Mumusoglu,S.; Polat,M.; Yarali Ozbek,I.; Esteves,S.C.; Humaidan,P.; Yarali,H.
    STUDY QUESTION: Do early-and mid-luteal serum progesterone (P4) levels impact ongoing pregnancy rates (OPRs) in fresh blastocyst transfer cycles using standard luteal phase support (LPS)? SUMMARY ANSWER: A drop in serum P4 level from oocyte pick-up (OPU) + 3 days to OPU + 5 days (negative ΔP4) is associated with a ∼2-fold decrease in OPRs. WHAT IS KNOWN ALREADY: In fresh embryo transfer cycles, significant inter-individual variation occurs in serum P4 levels during the luteal phase, possibly due to differences in endogenous P4 production after hCG trigger and/or differences in bioavailability of exogenously administered progesterone (P) via different routes. Although exogenous P may alleviate this drop in serum P4 in fresh transfer cycles, there is a paucity of data exploring the possible impact on reproductive outcomes of a reduction in serum P4 levels. STUDY DESIGN, SIZE, DURATION: Using a prospective cohort study design, following the initial enrollment of 558 consecutive patients, 340 fulfilled the inclusion and exclusion criteria and were included in the final analysis. The inclusion criteria were: (i) female age ≤40 years, (ii) BMI ≤35 kg/m2, (iii) retrieval of ≥3 oocytes irrespective of ovarian reserve, (iv) the use of a GnRH-Agonist or GnRH-Antagonist protocol with recombinant hCG triggering (6500 IU), (v) standard LPS and (vi) fresh blastocyst transfer. The exclusion criteria were: (i) triggering with GnRH-Agonist or GnRH-Agonist plus recombinant hCG (dual trigger), (ii) circulating P4 >1.5 ng/ml on the day of trigger and (iii) cleavage stage embryo transfer. Each patient was included only once. The primary outcome was ongoing pregnancy (OP), as defined by pregnancy ≥12 weeks of gestational age. PARTICIPANTS/MATERIALS, SETTING, METHODS: A GnRH-Agonist (n = 53) or GnRH-Antagonist (n = 287) protocol was used for ovarian stimulation. Vaginal progesterone gel (Crinone, 90 mg, 8%, Merck) once daily was used for LPS. Serum P4 levels were measured in all patients on five occasions: on the day of ovulation trigger, the day of OPU, OPU + 3 days, OPU + 5 days and OPU + 14 days; timing of blood sampling was standardized to be 3-5 h after the morning administration of vaginal progesterone gel. The delta P4 (ΔP4) level was calculated by subtracting the P4 level on the OPU + 3 days from the P4 level on the OPU + 5 days, resulting in either a positive or negative ΔP4. MAIN RESULTS AND THE ROLE OF CHANCE: The median P4 (min-max) on the day of triggering, day of OPU, OPU + 3 days, OPU + 5 days and OPU + 14 days were 0.83 ng/ml (0.18-1.42), 5.81 ng/ml (0.80-22.72), 80.00 ng/ml (22.91-161.05), 85.91 ng/ml (15.66-171.78) and 13.46 ng/ml (0.18-185.00), respectively. Serum P4 levels uniformly increased from the day of OPU to OPU + 3 days in all patients; however, from OPU + 3 days to OPU + 5 days, some patients had a decrease (negative ΔP4; n = 116; 34.1%), whereas others had an increase (positive ΔP4; n = 220; 64.7%), in circulating P4 levels. Although the median (min-max) P4 levels on the day of triggering, the day of OPU, and OPU + 3 days were comparable between the negative ΔP4 and positive ΔP4 groups, patients in the former group had significantly lower P4 levels on OPU + 5 days [69.67 ng/ml (15.66-150.02) versus 100.51 ng/ml (26.41-171.78); P < 0.001] and OPU + 14 days [8.28 ng/ml (0.28-157.00) versus 19.01 ng/ml (0.18-185.00), respectively; P < 0.001]. A drop in P4 level from OPU + 3 days to OPU + 5 days (negative ΔP4) was seen in approximately one-Third of patients and was associated with a significantly lower OPR when compared with positive ΔP4 counterparts [33.6% versus 49.1%, odds ratio (OR); 0.53, 95% CI; 0.33-0.84; P = 0.008]; this decrease in OPR was due to lower initial pregnancy rates rather than increased overall pregnancy loss rates. For negative ΔP4 patients, the magnitude of ΔP4 was a significant predictor of OP (adjusted AUC = 0.65; 95% CI; 0.59-0.71), with an optimum threshold of-8.73 ng/ml, sensitivity and specificity were 48.7% and 79.2%, respectively. BMI (OR; 1.128, 95% CI; 1.064-1.197) was the only significant predictor of having a negative ΔP4; the higher the BMI, the higher the risk of having a negative ΔP4. Among positive ΔP4 patients, the magnitude of ΔP4 was a weak predictor of OP (AUC = 0.56, 95% CI; 0.48-0.64). Logistic regression analysis showed that blastocyst morphology (OR; 5.686, 95% CI; 1.433-22.565; P = 0.013) and ΔP4 (OR; 1.013, 95% CI; 0.1001-1.024; P = 0.031), but not the serum P4 level on OPU + 5 days, were the independent predictors of OP. LIMITATIONS, REASONS FOR CAUTION: The physiological circadian pulsatile secretion of P4 during the mid-luteal phase is a limitation; however, blood sampling was standardized to reduce the impact of timing. WIDER IMPLICATIONS OF THE FINDINGS: Two measurements (OPU + 3 days and OPU + 5 days) of serum P4 may identify those patients with a drop in P4 (approximately one-Third of patients) associated with ∼2-fold lower OPRs. Rescuing these IVF cycles with additional P supplementation or adopting a blastocyst freeze-All policy should be tested in future randomized controlled trials. STUDY FUNDING/COMPETING INTEREST(S): None. S.C.E. declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. P.H. has received unrestricted research grants from MSD and Merck, as well as honoraria for lectures from MSD, Merck, Gedeon-Richter, Theramex, and IBSA. H.Y. declares receipt of honorarium for lectures from Merck, IBSA and research grants from Merck and Ferring. The remaining authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: The study was registered at clinical trials.gov (NCT04128436). © 2022 The Author(s). Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved.