P–377 Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H Yoshihara ◽  
M Sugiura-Ogasawara ◽  
T Kitaori ◽  
S Goto

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2% (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62% (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1: 40 dilution, the subsequent live birth rates were 71.34% (219/307) for the ANA-positive group and 70.67% (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707–1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41% (219/237) for the ANA-positive group and 92.04% (347/377) for the ANA-negative group (0.951, 0.517–1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62% (22/26) for the ANA-positive group, and 70.47% (544/772) for the ANA-negative group (0.434, 0.148–1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings: The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number Not applicable

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
H Yoshihara ◽  
M Sugiura-Ogasawara ◽  
T Kitaori ◽  
S Goto

Abstract Study question Can antinuclear antibody (ANA) affect the subsequent live birth rate in patients with recurrent pregnancy loss (RPL) who have no antiphospholipid antibodies (aPLs)? Summary answer ANA did not affect the pregnancy prognosis of RPL women. What is known already The prevalence of ANA is well-known to be higher in RPL patients. Our previous study found no difference in the live birth rates of ANA-positive and -negative patients who had no aPLs. Higher miscarriage rates were also reported in ANA-positive patients compared to ANA-negative patients with RPL. The RPL guidelines of the ESHRE state that “ANA testing can be considered for explanatory purposes.” However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. Study design, size, duration An observational cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1,108 patients with a history of 2 or more pregnancy losses. Participants/materials, setting, methods 4D-Ultrasound, hysterosalpingography, chromosome analysis for both partners, aPLs and blood tests for ANA and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining. Live birth rates were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid syndrome, an abnormal chromosome in either partner and a uterine anomaly. Main results and the role of chance The 994 patients were analyzed after excluding 40 with a uterine anomaly, 43 with a chromosome abnormality in either partner and 32 with APS. The rate of ANA-positive patients was 39.2 % (390/994) when the 1: 40 dilution result was positive. With a 1:160 dilution, the rate of ANA-positive patients was 3.62 % (36/994). The live birth rate was calculated for 798 patients, excluding 196 patients with unexplained RPL who had been treated with any medication. With the use of the 1 40 dilution, the subsequent live birth rates were 71.34 % (219/307) for the ANA-positive group and 70.67 % (347/491) for the ANA-negative group (OR, 95%CI; 0.968, 0.707-1.326). After excluding miscarriages with embryonic aneuploidy, chemical pregnancies and ectopic pregnancies, live birth rates were 92.41 % (219/237) for the ANA-positive group and 92.04 % (347/377) for the ANA-negative group (0.951, 0.517-1.747). Using the 1:160 dilution, the subsequent live birth rates were 84.62 % (22/26) for the ANA-positive group, and 70.47 % (544/772) for the ANA-negative group (0.434, 0.148-1.273). Subgroup analyses were performed for each pattern on immunofluorescence staining, but there was no significant difference in the live birth rate between the two groups. Limitations, reasons for caution The effectiveness of immunotherapies could not be evaluated. However, the results of this study suggest that it is not necessary. Wider implications of the findings The measurement of ANA might not be necessary for the screening of patients with RPL who have no features of collagen disease. Trial registration number not applicable


2021 ◽  
Vol 16 (3) ◽  
pp. 164-190
Author(s):  
John Lui Yovich ◽  
Shanthi Srinivasan ◽  
Mark Sillender ◽  
Shipra Gaur ◽  
Philip Rowlands ◽  
...  

This retrospective study examines the influence of recombinant growth hormone (rGH) and dehydroepiandrosterone (DHEA) adjuvants on oocyte numbers, embryo utilization and live births arising from 3637 autologous IVF±ICSI treatment cycles undertaken on 2376 women across ten years (2011-2020) within a pioneer Australian facility. Despite using an FSH-dosing algorithm enabling maximal doses up to 450 IU for women with reduced ovarian reserve, younger women had significantly higher mean numbers of oocytes recovered than older women ranging from 11.1 for women <35 years to 9.4 for women aged 35-39 years reducing to 6.5 for women aged 40-44 years and 4.1 for those aged ≥45 years (p<0.0001). Overall, the embryo utilization rate was 48.5% and live birth productivity rate was 35.4 % across all ages and neither rGH nor DHEA showed any benefit on these rates, in fact, those women with nil adjuvants showed the highest live birth rate per initiated cycle (44.94% overall: p<0.0001, and 55.2% for the youngest group: p<0.001). Embryo utilization was increased by rGH in those women aged 40-44 years who had low ovarian reserve (p<0.0001), but this benefit did not translate into any improvement in the live birth rate, in fact those women who did not use adjuvants had the highest overall birth rate (p<0.0001). Similarly, other factors known to cause a poor prognosis, including low IGF-1 profile, recurrent implantation failure, and low oocyte numbers at OPU, showed no improvement in embryo utilization nor in live births from the adjuvants. The relevance of embryo quality was examined on 1135 women whose residual embryos after a single fresh-embryo transfer failed to develop to a suitable grade for cryopreservation. From 1727 cycles such women often displayed an improved embryo utilization rate with both rGH, and with DHEA or combined rGH+DHEA. Even so, live birth rates were not improved by either of the adjuvants excepting young women <35 years using rGH without DHEA (p<0.05). Examining poor prognosis sub-groups, indicated both rGH and DHEA or combined rGH+DHEA consistently improved embryo utilization in those women with low ovarian reserve (p<0.0001), or those with low IGF-1 levels (p<0.0001) or with recurrent implantation failure (p<0.02). All the poor-prognosis sub-groups showed low live birth rates and, notwithstanding the improvements in embryo utilization, the live birth rates were not significantly improved by the adjuvants, albeit the rates were closer to the nil adjuvant groups (not significantly different).


2021 ◽  
Author(s):  
Hong Chen ◽  
Zhi qin Chen ◽  
Ernest Hung Yu Ng ◽  
zili sun ◽  
Zheng wang ◽  
...  

Abstract Background: The efficacy and reproductive outcomes of progestin primed ovarian stimulation protocol (PPOS) were previously compared to rarely used ovarian stimulation protocol and also the live birth rate were reported by per embryo transfer rather than cumulative live birth rates (CLBRs). Does the use of PPOS improve the cumulative live birth rates (CLBRs) and shorten time to live birth when compared to long GnRH agonist protocol in women with normal ovarian reserve?Methods: A retrospective cohort study was designed to include women aged<40 with normal ovarian reserve (regular menstrual cycles, FSH <10 IU/L, antral follicle count >5) undergoing IVF from January 2017 to December 2019. The primary outcome was cumulative live birth rates (CLBRs) within 18 months from the day of ovarian stimulation.Results: A total of 995 patients were analyzed. They used either PPOS (n=509) or long GnRH agonist (n=486) protocol at the discretion of the attending physicians. Both groups had almost comparable demographic and cycle stimulation characteristics except for duration of infertility which was shorter in the PPOS group. In the GnRH agonist group 372 cases (77%) completed fresh embryo transfer, resulting into 218 clinical pregnancies and 179 live birth. The clinical pregnancy rate, ongoing pregnancy, and live birth per transfer were 58.6%, 54.0%, 53.0% respectively. In the PPOS, no fresh transfer was carried out. During the study period, the total number of initiated FET cycles with thawed embryos was 665 in the PPOS group and 259 in the long agonist group. Of all FET cycles, a total of 206/662 (31.1%) cycles resulted in a live birth in the PPOS group versus 110/257 (42.8%) in the long agonist group (OR: 0.727; 95% CI: 0.607–0.871; p<0.001) .The implantation rate of total FET cycles was also lower in the PPOS group compared with that in the agonist group 293/1004 (29.2%) and 157/455 (34.5%) (OR: 0.846; 95% CI: 0.721–0.992; p= 0.041). Cumulative live birth rates after one complete IVF cycle including fresh and subsequent frozen embryo cycles within 18 months follow up were significantly lower in the PPOS group compared that in the long agonist group 206/509 (40.5%) and 307/486 (63.2%), respectively (OR: 0.641; 95% CI: 0.565-0.726). The average time from ovarian stimulation to pregnancy and live birth was significantly shorter in the long agonist group compared to the PPOS group (p<0.01) In Kaplan-Meier analysis, the cumulative incidence of ongoing pregnancy leading to live birth was significantly higher in the long agonist compared in the PPOS group(Log rank test, p<0.001). Cox regression analysis revealed stimulation protocol adopted was strongly associated with the cumulative live birth rate after adjusting other confounding factors (OR =1.917 (1.152-3.190), p=0.012) .Conclusion: Progestin primed ovarian stimulation was associated with a lower cumulative live birth rates and a longer time to pregnancy / live birth than the long agonist protocol in women with a normal ovarian reserve.


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


2019 ◽  
Vol 112 (3) ◽  
pp. e401 ◽  
Author(s):  
Julia G. Kim ◽  
Gayathree Murugappan ◽  
Ruth B. Lathi ◽  
Jonathan D. Kort ◽  
Brent M. Hanson ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Yakin ◽  
S Ertas ◽  
C Alatas ◽  
O Oktem ◽  
B Urman

Abstract Study question Does elevated late-follicular phase estrogen and progesterone levels have an impact on blastocyst utilization and/or cumulative live birth rates in freeze-all cycles? Summary answer High estrogen or progesterone on the day of ovulation trigger is associated with poor blastocyst utilization but comparable cumulative live birth rates in freeze-all cycles. What is known already Several studies suggest impaired clinical outcome in cycles with high estrogen (&gt;3500 pg/ml) or progesterone (&gt;1.5 ng/ml) levels. However, these data were derived from cycles where top-quality embryo(s) were transferred in the fresh cycle and surplus embryos were frozen. These findings might be confounded by alterations in endometrial receptivity. Freeze-all cycles might provide a better model to assess the impact of high late-follicular estrogen or progesterone levels on laboratory and clinical outcome. Study design, size, duration We performed a retrospective cohort study of all IVF cycles (n = 712) between 2016 and 2018 where the entire cohort of embryos was cryopreserved at the blastocyst stage. After excluding cases with &lt;4 oocytes or preimplantation genetic test, the study group comprised 459 women who had 699 frozen-thawed embryo transfer cycles. Participants/materials, setting, methods Women were classified into four groups by the indication for freeze-all strategy as elevated progesterone (high P, n = 61), high estrogen (high E, n = 224), elective freezing (elective, n = 114) and tubal-endometrial pathologies (TEP, n = 60). The primary outcome was the cumulative live birth rate in subsequent thaw-transfer cycles and the secondary outcome was the blastocyst utilization rate. Groups were compared using ANOVA and Cox regression analyses to adjust for confounding variables. Main results and the role of chance The mean age of the study group was 32.8 ± 5.3 years, total number of oocytes and cryopreserved blastocysts were 15.0±7.6 and 4.2±3.0, respectively. The high-E group was younger (31.5 ± 5.2 years) and had higher peak E2 levels (4078.9 ± 588.4 pg/ml), number of oocytes (19.7 ± 7.0), cryopreserved embryos (5.3 ± 3.3) and transfer cycles (2.3 ± 1.4) than the other groups. Blastocyst utilization rate was significantly lower (40.4%) compared to elective freezing (53.6%) and TEP groups (55.7%) (both p = 0.001). The high-P group had higher peak progesterone levels (2.1 ± 0.5 ng/ml, p = 0.001), number of oocytes (14.0 ± 5.2) and frozen embryos (4.1 ± 3.5) compared to elective and TEP groups (both p = 0.04). Blastocyst utilization rate was lower (45.7%) than elective freezing and TEP groups but the difference lacked statistical significance (p = 0.33 and p = 0.21, respectively). Cumulative live birth rates were 42.6% in high-P, 59.8% in high-E, 44.7% in elective freezing and 46.7% in TEP groups. Significant predictors of cumulative live birth were female age (aHR: 0.97, 95%CI:0.95–0.99, p = 0.02) and number of frozen blastocysts (aHR:1.05, 95%CI:1.01–1.10), p = 0.02). When adjusted for these confounders, the cumulative live birth rate was not associated with high-E (aHR: 0.86, 95%CI:0.56–1.31) or high-P (aHR: 0.76,95%CI:0.44–1.32). Limitations, reasons for caution This was a retrospective study with small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings: While lower blastocyst utilization rates are observed in women high late-follicular estradiol or progesterone levels, cumulative live birth rates in subsequent thaw-transfer cycles were not impaired. However, unfavorable outcome parameters observed in women with elevated progesterone deserve further research. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Hammond ◽  
Y Liu ◽  
F Xu ◽  
G Liu ◽  
H Xi ◽  
...  

Abstract Study question What is the live birth rate after single, low-grade blastocyst (LGB) transfer? Summary answer The live birth rate for LGBs is 28%, ranging between 15–31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. What is known already Live birth rates following LGB transfer are varied and have been reported to be in the range of 5–39%. However, these estimates are inaccurate as studies investigating live birth rates following LGB transfer are inherently limited by sample size (n = 10–440 for LGB transfers) due to LGBs being ranked last for transfer. Further, these studies are heterogenous with varied LGB definitions and design. Collating LGB live birth data from multiple clinics is warranted to obtain sufficient numbers of LGB transfers to establish reliable live birth rates, and to allow for delineation of different LGB subgroups, including blastocyst age and female age. Study design, size, duration We performed a multicentre, multinational retrospective cohort study in 9 IVF centres in China and New Zealand from 2012 to 2019. We studied the outcome of 6966 single blastocyst transfer cycles on days 5–7 (fresh and frozen) according to blastocyst grade, including 875 transfers from LGBs (&lt;3bb, this being the threshold typically applied to LGB studies). Blastocysts with expansion stage 1 or 2 (early blastocysts) were excluded. Participants/materials, setting, methods The main outcome measured was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n = 3849, aa, ab and ba), moderate-grade blastocysts (MGBs; n = 2242, bb) and LGBs (n = 875, ac, ca, bc, cb and cc) and live birth rates compared using the Pearson Chi-squared test. A logistic regression analysis explored the relationship between blastocyst grade and live birth after adjustment for the confounders: clinic, female age, expansion stage, and blastocyst age. Main results and the role of chance The live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p &lt; 0.0001). Within the LGB group, the highest live birth rates were for grade c TE (30%) and the lowest were for grade c ICM (19%). The lowest combined grade (cc) maintained a 15% live birth rate (n = 7/48). After accounting for confounding factors, including female age and blastocyst characteristics, the odds of live birth were 2.33 (95% CI = 1.88–2.89) for GGBs compared to LGBs and 1.56 (95% CI = 1.28–1.92) for MGBs compared to LGBs following fresh and frozen blastocyst transfers (p &lt; 0.0001, odds ratios confirmed in exclusively frozen blastocyst transfer cycles). When stratified by individual ICM and TE grade, the odds of live birth according to ICM grade were 1.31 (a versus b; 95% CI = 1.15–1.48), 2.82 (a versus c; 95% CI = 1.91–4.18) and 2.16 (b versus c; 95% CI = 1.48–3.16; all p &lt; 0.0001). The odds of live birth according to TE grade were 1.33 (a versus b; 95% CI = 1.17–1.50, p &lt; 0.0001), 1.85 (a versus c; 95% CI = 1.45–2.34, p &lt; 0.0001) and 1.39 (b versus c; 95% CI = 1.12–1.73, p = 0.0024). Limitations, reasons for caution Despite the large multicentre design of the study, analyses of transfers occurring within the smallest subsets of the LGB group were limited by sample size. The study was not randomised and had a retrospective character. Wider implications of the findings: LGBs maintain satisfactory live birth rates (averaging 28%) in the general IVF population. Even those in the lowest grading tier maintain modest live birth rates (15%; cc). It is recommended that LGBs not be universally discarded, and instead considered for subsequent frozen embryo transfer to maximize cumulative live birth rates. Trial registration number Not applicable


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