The Perspective of Freeze-All in Assisted Reproductive Technologies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Reproductive Medicine & Andrology".

Deadline for manuscript submissions: closed (25 April 2023) | Viewed by 14939

Special Issue Editors


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Guest Editor
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Interests: reproductive medicine; reproductive genetics; reproductive endocrinology

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Co-Guest Editor
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Interests: reproductive medicine; reproductive genetics; reproductive endocrinology

Special Issue Information

Dear Colleagues,

The prevalence of freeze-all policy (or elective embryo transfer) in reproductive medicine is rising globally. Its advantages are mainly shown in terms of avoiding the deleterious effects of ovarian stimulation on embryo–endometrium synchrony and the risk of ovarian hyperstimulation syndrome. Based on this strategy, novel protocols have been developed; these include progestin-primed ovarian stimulation (PPOS) and double ovarian stimulation, which provide more flexible approaches. However, there is still a lack of worldwide consensus on the pros and cons of freeze-all. Although a great deal of experience has been accumulated in clinical practice, evidence gaps persist at all points in translating the strategy to efficacious therapies. For instance, more research is needed to understand the molecular mechanism of vitrification, to confirm the efficacy of non-classical protocols of ovarian stimulation, to balance the costs and benefits in the field of health management, and to evaluate the long-term safety of vitrification for offspring. The scope of this Special Issue is to provide an overview of recent advances and prospective developments in the freeze-all field. Therefore, researchers in the field of reproductive medicine are encouraged to submit original articles or reviews to this Special Issue (case reports and short reviews are not accepted).

Prof. Dr. Yanping Kuang
Dr. Qiuju Chen
Guest Editors

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Keywords

  • assisted reproductive technology
  • freeze-all policy
  • elective embryo transfer
  • vitrification
  • progestin-primed ovarian stimulation
  • double ovarian stimulation
  • health economics
  • live birth
  • long-term safety of offspring

Published Papers (8 papers)

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Research

11 pages, 457 KiB  
Article
Pregnancy Outcomes of Freeze-All versus Fresh Embryo Transfer in Women with Adenomyosis: A Retrospective Study
by Qiaoli Zhang, Qiaoyuan Chen, Tianhe Li, Zhaoxia Jia, Xiaomeng Bu, Yanjun Liu, Shuyu Wang and Ying Liu
J. Clin. Med. 2023, 12(5), 1740; https://doi.org/10.3390/jcm12051740 - 21 Feb 2023
Viewed by 1619
Abstract
Adenomyosis has been associated with adverse fertility and pregnancy outcomes, and its impact on the outcomes of in vitro fertilization (IVF) has received much attention. It is controversial whether the freeze-all strategy is better than fresh embryo transfer (ET) in women with adenomyosis. [...] Read more.
Adenomyosis has been associated with adverse fertility and pregnancy outcomes, and its impact on the outcomes of in vitro fertilization (IVF) has received much attention. It is controversial whether the freeze-all strategy is better than fresh embryo transfer (ET) in women with adenomyosis. Women with adenomyosis were enrolled in this retrospective study from January 2018 to December 2021 and were divided into two groups: freeze-all (n = 98) and fresh ET (n = 91). Data analysis showed that freeze-all ET was associated with a lower rate of premature rupture of membranes (PROM) compared with fresh ET (1.0% vs. 6.6%, p = 0.042; adjusted OR 0.17 (0.01–2.50), p = 0.194). Freeze-all ET also had a lower risk of low birth weight compared with fresh ET (1.1% vs. 7.0%, p = 0.049; adjusted OR 0.54 (0.04–7.47), p = 0.642). There was a nonsignificant trend toward a lower miscarriage rate in freeze-all ET (8.9% vs. 11.6%; p = 0.549). The live birth rate was comparable in the two groups (19.1% vs. 27.1%; p = 0.212). The freeze-all ET strategy does not improve pregnancy outcomes for all patients with adenomyosis and may be more appropriate for certain patients. Further large-scale prospective studies are needed to confirm this result. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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9 pages, 478 KiB  
Article
The Impact of Late Follicular Phase Progesterone Elevation on Cumulative Live Birth Rate and Embryo Quality in 4072 Freeze-All Cycles
by Ling Huang, Sunxing Huang, Yangxing Wen, Xiubing Zhang, Xiaokun Hu, Rihan Wu, Minghui Chen and Canquan Zhou
J. Clin. Med. 2022, 11(24), 7300; https://doi.org/10.3390/jcm11247300 - 08 Dec 2022
Viewed by 995
Abstract
Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total [...] Read more.
Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total of 4072 patients were reviewed. All patients used the freeze-all strategy. Multivariate regression analyses were used to assess the association of progesterone levels with both cumulative live birth and embryo quality. There was no significant difference in the cumulative live birth rate between the groups with progesterone level <1.5 ng/mL and ≥1.5 ng/mL. The progesterone level was not associated with cumulative live birth and embryo quality. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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11 pages, 913 KiB  
Article
Preventing Growth Stagnation and Premature LH Surge Are the Keys to Obtaining a Viable Embryo in Monofollicular IVF Cycles: A Retrospective Cohort Study
by Xiaoyan Guo, Xiaoping Zhu, Xiangli Wu, Yiqi Yu, Ling Zhang and Jing Shu
J. Clin. Med. 2022, 11(23), 7140; https://doi.org/10.3390/jcm11237140 - 01 Dec 2022
Cited by 1 | Viewed by 2712
Abstract
How LH levels influenced the outcomes of monofollicular IVF cycles using different stimulation protocols was controversial. In this single-center, retrospective study, we analyzed 815 monofollicular IVF cycles between 2016–2022 using natural cycle (NC), medroxyprogesterone acetate (MPA) or clomiphene citrate (CC) in addition to [...] Read more.
How LH levels influenced the outcomes of monofollicular IVF cycles using different stimulation protocols was controversial. In this single-center, retrospective study, we analyzed 815 monofollicular IVF cycles between 2016–2022 using natural cycle (NC), medroxyprogesterone acetate (MPA) or clomiphene citrate (CC) in addition to human menopausal gonadotropin (hMG), with or without GnRH antagonist. A viable embryo was obtained in 35.7% of all cycles. Growth stagnation and premature LH surge are two markedly negative factors for obtaining viable embryos (odds ratios of 0.12 [0.08–0.65], p < 0.0001 and 0.33 [0.26,0.42], p < 0.0001, respectively). NC/hMG cycles are prone to premature LH surge (40.4%), yielding a significantly lower opportunity of obtaining embryos (24.7%, p = 0.029). The administration of GnRH antagonist on the background of MPA resulted in a significant decrease in LH levels (from 2.26 IU/L to −0.89 IU/L relative to baseline, p = 0.000214), leading to a higher risk of growth stagnation (18.6%, p = 0.007). We hypothesized that the abrupt decline of LH might increase the risk of apoptosis in granulosa cells. We proposed a “marginal effect” framework to emphasize that the change of LH was the key to its bioactivity, rather than the traditional “window” concept with fixed cutoff values of a threshold and a ceiling. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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10 pages, 233 KiB  
Article
Pregnancy Outcomes in Double Stimulation versus Two Consecutive Mild Stimulations for IVF in Poor Ovarian Responders
by Jingzhe Li, Shiqing Lyu, Shijian Lyu and Minzhi Gao
J. Clin. Med. 2022, 11(22), 6780; https://doi.org/10.3390/jcm11226780 - 16 Nov 2022
Cited by 3 | Viewed by 2252
Abstract
To compare pregnancy outcomes between double stimulation (DouStim) and two consecutive mild stimulations in poor ovarian responders, this study retrospectively analyzed 281 patients diagnosed as having poor ovarian response (POR) who underwent oocytes retrieval for in vitro fertilization (IVF) or intracytoplasmic sperm injection [...] Read more.
To compare pregnancy outcomes between double stimulation (DouStim) and two consecutive mild stimulations in poor ovarian responders, this study retrospectively analyzed 281 patients diagnosed as having poor ovarian response (POR) who underwent oocytes retrieval for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) from January 2018 to December 2020. They were divided into two groups: the DouStim group (n = 89) and the two consecutive mild stimulations group (n = 192). The results illustrated that there were no significant differences in the number of oocytes and 2PNs between the two groups. The number of frozen embryos [1 (0, 2) versus 1(0, 2)] was significantly lower and the proportion of patients without frozen embryos (39.3% versus 26.0%) was significantly higher in the DouStim group than in the two consecutive mild stimulations group (p < 0.05). There were no significant differences in the clinical pregnancy rate (CPR) and the cumulative live birth rate (CLBR) between the two groups (p > 0.05). The intra-subgroup comparison showed that in young POR patients under 35 years old, there were no significant differences in clinical indicators and pregnancy outcomes (p > 0.05). In elderly POR patients aged 35 years and above, the number of frozen embryos [1 (0, 1.5) versus 1 (0.25, 2)] (p < 0.01) was significantly lower in the DouStim group than in the two consecutive mild stimulations group, but the pregnancy outcomes were not significantly different (p > 0.05). In conclusion, the DouStim protocol is inferior to the two consecutive mild stimulations protocol in terms of the number of frozen embryos, which mainly occurs in elderly patients, but there is no difference in pregnancy outcomes between the two protocols. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
11 pages, 242 KiB  
Article
Effects of Different Endometrial Preparation Regimens during IVF on Incidence of Ischemic Placental Disease for FET Cycles
by Yingjie Wang, Qiuju Chen and Yun Wang
J. Clin. Med. 2022, 11(21), 6506; https://doi.org/10.3390/jcm11216506 - 02 Nov 2022
Cited by 1 | Viewed by 1171
Abstract
We conducted this retrospective cohort study aiming to compare the different pregnancy outcomes of endometrial preparation regimens on ischemic placental disease in a frozen embryo transfer cycle. The study included a total of 9351 women who had undergone therapy at our single tertiary [...] Read more.
We conducted this retrospective cohort study aiming to compare the different pregnancy outcomes of endometrial preparation regimens on ischemic placental disease in a frozen embryo transfer cycle. The study included a total of 9351 women who had undergone therapy at our single tertiary hospital from January 2015 to July 2020. The women were divided into three groups depending on their endometrial regimens: natural cycle, stimulation cycle, hormone replacement therapy cycle. The data were analyzed after propensity score matching, then we used multiple linear regression to study the relationship between ischemic placental disease and endometrial regimens, adjusted by confounding factors including age, body mass index, and score of propensity score matching. We performed univariate logistic regression, as well as multivariate logistic regression for ischemic placental disease, small for gestational age infant, placental abruption. and pre-eclampsia, respectively, listing the odds ratio and p-values in the table. As a result, risk of ischemic placental disease and small for gestational age infant were detected as higher in stimulation cycles compared to natural cycles before or after adjustment. Hormone replacement therapy cycles conferred a higher risk of pre-eclampsia and preterm delivery compared to natural cycles. No difference was found between stimulation cycles and hormone replacement therapy cycles, regardless of whether they are adjusted or not. In summary, more pharmacological intervention in endometrial preparation was associated with a higher risk of ischemic placental disease related symptoms than natural cycles for endometrial preparation in women undergoing frozen embryo transfer. Our findings supported that minimizing pharmacological interventions during endometrial preparation when conditions permit has positive implications for improving pregnancy outcomes. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
11 pages, 594 KiB  
Article
Pregnancy Outcomes after Frozen Embryo Transfer and Fresh Embryo Transfer in Women of Advanced Maternal Age: Single-Center Experience
by Yao Chen, Jianbo Zhou, Yandong Chen, Jihong Yang, Yingying Hao, Ting Feng, Ruizhi Feng and Yun Qian
J. Clin. Med. 2022, 11(21), 6395; https://doi.org/10.3390/jcm11216395 - 28 Oct 2022
Cited by 3 | Viewed by 2095
Abstract
Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first [...] Read more.
Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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11 pages, 810 KiB  
Article
Comparable Pregnancy Loss and Neonatal Birthweights in Frozen Embryo Transfer Cycles Using Vitrified Embryos from Progestin-Primed Ovarian Stimulation and GnRH Analogue Protocols: A Retrospective Cohort Study
by Weiran Chai, Maokun Liao, Guang’en Feng, Mengjie Wei, Wentao Shi, Yun Wang and Qiuju Chen
J. Clin. Med. 2022, 11(20), 6151; https://doi.org/10.3390/jcm11206151 - 19 Oct 2022
Cited by 1 | Viewed by 1175
Abstract
Background: The potential correlation between progestin-primed ovarian stimulation (PPOS) and the risk of compromised embryo competence still lacks sound evidence. Methods: A large retrospective cohort study was used to compare the incidence of pregnancy loss and neonatal birthweights in frozen embryo transfer (FET) [...] Read more.
Background: The potential correlation between progestin-primed ovarian stimulation (PPOS) and the risk of compromised embryo competence still lacks sound evidence. Methods: A large retrospective cohort study was used to compare the incidence of pregnancy loss and neonatal birthweights in frozen embryo transfer (FET) cycles using embryos from PPOS and GnRH analogue protocols. Propensity matched scores were used to balance the baseline confounders. Results: A total of 5744 matched cycles with positive hCG test were included to compare the pregnancy outcomes. The incidence of pregnancy loss was similar between PPOS and GnRH analogue groups (19.2% vs. 18.4%, RR 1.02 (0.97, 1.06), p > 0.05). The neonatal birthweights were comparable between two groups, respectively, for singleton births (3337.0 ± 494.4 g vs. 3346.0 ± 515.5 g) and in twin births (2496.8 ± 429.2 g vs. 2533.2 ± 424.2 g) (p > 0.05). Conclusions: The similar incidence of pregnancy loss and neonatal birthweights in FET cycles using embryos from PPOS provided us with a more complete picture about the safety of PPOS. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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9 pages, 827 KiB  
Article
Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study
by Zhijie Hu, Danjun Li, Qiuju Chen, Weiran Chai, Qifeng Lyu, Renfei Cai, Yanping Kuang and Xuefeng Lu
J. Clin. Med. 2022, 11(12), 3386; https://doi.org/10.3390/jcm11123386 - 13 Jun 2022
Cited by 2 | Viewed by 1801
Abstract
Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF–ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this [...] Read more.
Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF–ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022. Throughout the study, the total EP rate was 2.09% (336/16,048), 2.16% (82/3803) in the ET group, and 2.07% (254/12,245) in the FET group. After adjustment for age, infertility causes, and other confounding factors, logistic regression results showed no statistical difference in EP rates between FET and ET groups (odds ratio (OR) 0.93 (0.71–1.22), p > 0.05). However, among the 3808 patients who underwent fresh ET cycles, the OR for EP was significantly lower in the long agonist protocol group than in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol group (OR 0.45 (0.22–0.93), p < 0.05). Through a large retrospective study, we demonstrated a slightly lower EP rate in FET cycles than in fresh ET cycles, but there was no significant difference. The long agonist protocol in ET cycles had a significantly lower risk of EP than the GnRH-ant protocol. Full article
(This article belongs to the Special Issue The Perspective of Freeze-All in Assisted Reproductive Technologies)
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