O-093 Male translocations in recurrent pregnancy loss: Natural conception versus PGD treatment: what is the right option?: A systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Cardenas Armas ◽  
M Duran-Retamal ◽  
R Odia ◽  
S Cawood ◽  
E Drew ◽  
...  

Abstract Study question Does PGD treatment in couples with a history of RPL due to male translocations improve the outcome, increasing LBR and reducing miscarriage rate and time taken to live birth? Summary answer Live birth rate is significantly increased, miscarriage rate is significantly reduced using PGD. Time taken to achieve live birth rate is shorter in PGD treatment. What is known already Reciprocal translocation are the most common structural rearrangement in infertile men. The specific chromosomes and breakpoints involved might play an important role, often expressed as abnormal semen parameters or repeated pregnancy loss (RPL). The genetic counselling of these men remains challenging. Previous studies and meta-analysis performed showed no difference in live birth rate when comparing natural conception versus PGD treatment. However, the difference in miscarriage rate and time to live birth between PGD and natural conception has not been reported before in the medical literature. Study design, size, duration A systematic review of the literature was ­conducted through MEDLINE, EMBASE, and the Cochrane database up until December 2020. A comprehensive search yield 287 articles, 25 of which were included for abstract reading, finally, six were included in the meta-analysis. Participants/materials, setting, methods The six selected articles, reported on Live birth rate (LBR), miscarriage rate and time to live birth (TTLB) for natural conception compared to PGD for the same cohort of patients. All of the included articles were of retrospective design. The primary outcome was the comparison in LBR and the second outcome was the analysis in miscarriage rate and TTLB in the PGD group versus natural conception. Main results and the role of chance A total of 1438 couples that conceived naturally, had a LBR of 22.46%, compared with 43,17% among 681 couples that underwent PGD (0.53 95% CI (0.43-0.65) p o < 0,00001). The six articles included in this meta-analysis had significant homogeneity (I2 = 96%). Comparison of miscarriage rates, natural conception represented 1339 miscarriages out of 1836 pregnancies, in comparison with 44 miscarriages out of 558 pregnancies achieved through PGD. The OR showed a 10 fold increase risk of miscarriage when conceiving naturally in couples with a male translocation (10.18; 95% CI (2.88-36.04) p = 0.0003). Regarding TTLB, the difference was not statistically significant, however it did reflect that PGD patients will have a shorter TTLB (3.56 95% CI (-0.88-8.00)p = 0.12). One of the studies included, took into account the waiting list to access PGD funding, prolonging therefore the TTLB in the PGD group. Limitations, reasons for caution The main limitation of this study is the low number of studies. TTLB should be interpreted with caution given that one of the articles included the time of the waiting lists. More studies could demonstrate a shorter time period for these couples to conceive and have a successful ongoing pregnancy. Wider implications of the findings First study to demonstrate the value of PGD in decreasing miscarriage rates in couples with RPL. Specially when counselling couples with history of RPL with male translocations. PGD should be offered in these couples to improve the outcome, and to diminish the physical, emotional and sequelae of RPL and TOP. Trial registration number not applicable

Author(s):  
Peng-Sheng Zheng ◽  
Shan Li ◽  
Jing Jing He

Background Parental abnormal chromosomal karyotypes are considered as reasons for recurrent pregnancy loss. Objective This systematic meta-analysis evaluated the current evidence on pregnancy outcomes amongst couples with abnormal versus normal chromosomal karyotypes. Search strategy Two independent reviewers screened titles and abstracts identified in EMBASE and PubMed from inception to January 2021. Selection criteria Studies were included if they provided a description of pregnancy outcomes of parental chromosomal abnormality. Data collection and analysis Random effects meta-analysis was used to compare odds of pregnancy outcomes associated with noncarriers and carriers. Main results A significantly lower first pregnancy live birth rate (FPLBR) was found in carriers than in noncarriers with RPL (OR: 0.55; 95% CI: 0.46-0.65; p<0.00001). Regarding FPLBR between translocation or inversion carriers and noncarriers, a markedly decreased FPLBR was found in translocation (OR: 0.44; 95% CI: 0.31–0.61; p<0.00001) but not inversion carriers. The accumulated live birth rate (ALBR) (OR: 0.96; 95% CI: 0.90–1.03; p=0.26) was similar, while the miscarriage rate (MR) of accumulated pregnancies (OR: 2.21; 95% CI: 1.69–2.89; p<0.00001) was significantly higher in the carriers than in noncarriers with RPL. The ALBR was not significant (OR: 1.82; 95% CI: 0.38–8.71; p=0.45) but the MR (OR: 5.75; 95% CI: 2.57–12.86; p<0.0001) was markedly lower for carriers who choose PGD than natural conception. Conclusions Carriers with RPL had higher risk of miscarriage but obtained a satisfying pregnancy outcome through multiple attempts. No sufficient evidence was found PGD could enhance the ALBR but it was an alternative to decrease the MR.


2020 ◽  
Vol 9 (9) ◽  
pp. 2857
Author(s):  
Mónica Sánchez-Santiuste ◽  
Mar Ríos ◽  
Laura Calles ◽  
Reyes de la Cuesta ◽  
Virginia Engels ◽  
...  

To compare the obstetric results achieved after hysteroscopic office metroplasty (HOME-DU) in infertile and recurrent pregnancy loss (RPL) patients diagnosed with dysmorphic uterus, women hysteroscopically diagnosed with dysmorphic uterus who underwent uterine-enlargement metroplasty were prospectively enrolled from June 2016 until April 2020. Patients were followed up and obstetric outcomes were recorded (pregnancy and live birth rate). Sixty-three women (30 infertile; 33 RPL) were enrolled, of which 48 became pregnant post-HOME-DU, with an overall pregnancy rate of 76.2% (66.7% among infertile participants; 84.9% among those with RPL). Overall, 64.3% (n = 36/63) achieved live birth. Among infertile women, 62.07% (n = 18/29) achieved live birth, as well as 66.7% of women with RPL (n = 18/27). The difference in live birth rates between both cohorts was 4.6% (p > 0.05). The rate of miscarriage amongst infertile patients was 3.3% (n = 1/30) and 12.1% amongst women with RPL (n = 4/33). Office metroplasty via the HOME-DU technique improves obstetric results (namely increasing live birth rate) in patients with dysmorphic uterus and a history of reproductive failure. No significant difference was found in the clinical efficacy of HOME-DU in infertile and RPL patients.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kai-Lun Hu ◽  
Siwen Wang ◽  
Xiaohang Ye ◽  
Dan Zhang ◽  
Sarah Hunt

Abstract Background Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. Methods This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. Results A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I2 = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I2 = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I2 = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I2 = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I2 = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I2 = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I2 = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I2 = 0%, low evidence). Conclusion Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. Trial registration CRD42020204452.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
G Spagnol ◽  
G Bonaldo ◽  
M Marchetti ◽  
A Vitagliano ◽  
A S Laganà ◽  
...  

Abstract Study question How does the septate uterus and his metroplasty influence pregnancy rate (PR), live birth rate (LBR), spontaneous abortion rates (SA) and preterm labour rates (PL)? Summary answer Uterine septum is associated with a poor reproductive outcome. Metroplasty reduce the rate of SA but non-conclusive evidence can be extrapolated about PR and PL. What is known already Different studies evaluated the correlation between uterine septum and reproductive outcomes. On one hand, studies reported its association with poor obstetrics outcomes. On the other hand, recent studies raised doubts about the effectiveness of septum metroplasty to improve reproductive outcomes, although recent position papers continue to propose metroplasty in patients with a septate uterus and a history of infertility or miscarriages. Debate is still ongoing on reproductive outcomes of uterine septum on infertile patients and especially on patients with recurrent miscarriage, leading to an unanswered question whether or not these women should be treated. Study design, size, duration Systematic review and meta-analysis of published studies that evaluated the clinical impact of uterine septum and its metroplasty on reproductive and obstetrics outcomes. The meta-analysis included study with infertile patients or patients with a history of recurrent miscarriage. Searches were conducted using the following search terms: uterine septum, septate uterus, metroplasty, pregnancy rate, live birth rate, spontaneous miscarriage, infertility, preterm delivery. Primary outcomes were PR and LBR. Secondary outcomes were SA and PL. Participants/materials, setting, methods The meta-analysis was written following the PRISMA guidelines. Fifty-nine full-text articles were preselected based on title and abstract. Endpoints were evaluated in three subgroups: 1) infertile/recurrent miscarriage patients with septum versus no septum 2) infertile/recurrent miscarriage patients with treated versus untreated septum 3) infertile/recurrent miscarriage patients before-after septum removal. Odds-ratios (OR) with 95% confidence intervals (CI) were calculated for outcome measures. Random-effect meta-analysis was performed and a p-value less than 0.05 was considered statistically significant. Main results and the role of chance Data from 37 articles were extracted. In the first subgroup (10 studies), a lower PR and LBR were associated with septate uterus vs. controls, respectively (OR 0.39, 95% CI 0.26 to 0.58; p &lt; 0.000; low-heterogeneity and OR 0.21, 95% CI 0.12 to 0.39; p &lt; 0.0001; small-heterogeneity) and a higher proportion of SA and PL was associated with septate uterus vs. controls, respectively (OR 4.17, 95% CI 2.83 to 6.15; p &lt; 0.000; moderate-heterogeneity and OR 2.18, 95% CI 1.27 to 3.76; p = 0.005; low-heterogeneity). In the second subgroup (8 studies), PR and PL were not different in removed vs. unremoved septum, respectively (OR 1.10, 95% CI 0.49 to 2.49; p = 0.82; moderate heterogeneity and OR 0.44, 95% CI 0.18 to 1.08; p = 0.08;low-heterogeneity) and a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.40, 95% CI 0.17 to 0.95; p = 0.001; substantial-heterogeneity). In the third subgroup (19 studies), the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93 to 82.13; p &lt; 0.0001; moderate-heterogeneity) and the proportion of SA and PL was lower after the removal of septum, respectively (OR 0.02, 95% CI 0.02 to 0.04; p &lt; 0.000; moderate-heterogeneity and OR 0.05, 95% CI 0.03 to 0.08; p = &lt;0.000; low-heterogeneity). Limitations, reasons for caution The present meta-analysis is limited by the observational design of included studies because, in literature, there are no prospective randomized controlled trials (RCTs). In the second and third subgroup of analysis clinical heterogeneity within and between studies represents another limitation. Wider implications of the findings The results of this meta-analysis confirm the detrimental effect of uterine septum on PR, LBR, SA and PL. Its treatment seems to reduce the rate of SA. Metroplasty should still be considered as good clinical practice in patients with a history of infertility and recurrent abortion. Trial registration number Not applicable © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: [email protected].


2017 ◽  
Vol 108 (3) ◽  
pp. e34
Author(s):  
T.C. Plowden ◽  
M.T. Connell ◽  
P. Mendola ◽  
K. Kim ◽  
C. Nobles ◽  
...  

2019 ◽  
Vol 34 (12) ◽  
pp. 2340-2348 ◽  
Author(s):  
Takeshi Sato ◽  
Mayumi Sugiura-Ogasawara ◽  
Fumiko Ozawa ◽  
Toshiyuki Yamamoto ◽  
Takema Kato ◽  
...  

Abstract STUDY QUESTION Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? SUMMARY ANSWER PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. WHAT IS KNOWN ALREADY PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40–50% and 5–25% in patients with RPL, respectively. STUDY DESIGN, SIZE, DURATION A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35–36, 37–38, 39–40 or 41–42 years) were selected for PGT-A groups. PARTICIPANTS/MATERIALS, SETTING, METHODS All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. MAIN RESULT AND THE ROLE OF CHANCE There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16–13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28–10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02–0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03–0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. LIMITATIONS, REASONS FOR CAUTION The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. WIDER IMPLICATION OF THE FINDINGS A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A


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