Optimal Ovulation Trigger–Oocyte Pickup Interval in Progestin-Primed Ovarian Stimulation Protocol: A Retrospective Study Using Propensity Score Matching

Shen, Xi; Long, Hui; Guo, Wei; Gao, Hongyuan; Cai, Renfei; Jin, Wei; Zhou, Yan; Zhang, Shaozhen; Wang, Yun; Lyu, Qifeng; Wang, Li; Kuang, Yanping

doi:10.3389/fendo.2019.00694

Cited by 7 publications

(8 citation statements)

References 31 publications

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“…We could only verify the function of PPOS in delaying ovulation from the distribution of ovulation trigger-OPU time intervals with oocyte retrieval rate (> 70%) and mature oocyte rate (> 80%). And the mature oocyte rate and implantation rate of patients using PPOS was signi cantly higher in the groups with prolonged trigger-OPU interval 11 .…”

Section: Discussionmentioning

confidence: 89%

“…Furthermore, our former clinical research 11 in patients with PPOS protocol, which used the propensity score to auto-match patients with the homogeneous clinical characteristics among three trigger-OPU interval groups (group 1: 35.6-36.4h; group 2: 36.4-37.1h; group 3: 37.1-37.8 h), found that the trigger-OPU interval within groups 2 and 3 had signi cantly higher mature oocyte rates (84.54% vs. 84.60% vs.82.34%, p = 0.002) and implantation rates (34.17% vs. 34.37% vs. 29.61%, p < 0.05) than group 1. A relative prolonged ovulation trigger-OPU interval (36.4-37.8 h) is optimal for most patients using a PPOS protocol.…”

Section: Discussionmentioning

confidence: 99%

“…From initial "Luteal-phase ovarian stimulation" in 2013 1 , "double stimulations during the follicular and luteal phases (Shanghai protocol)" in 2014 8 , "the prototype of PPOS" in 2015 9 to "the exible PPOS" in 2016 10 , we nd that all of them could effectively inhibit the premature LH surge and ovulation. Furthermore, the patients in the prolonged ovulation trigger-oocyte pickup (OPU) time interval group (36.4-37.1h, 37.1-37.8h) had signi cantly higher mature oocyte rate, implantation rate and live birth rate per transfer than the earlier group (35.6-36.4h) 11 . These results indicate that PPOS inhibits the LH level before trigger and might delay the process of ovulation, which is di cult to be veri ed in the clinic.…”

Section: Introductionmentioning

confidence: 99%

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A delayed ovulation of Progestin-Primed Ovarian Stimulation (PPOS) by down-regulating the LHCGR/PGR pathway

Xie

Guo

Shen

et al. 2022

Preprint

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PPOS as a new clinic ovulation stimulation protocol, its role in ovulation and regulatory mechanism is not clear. The clinical PPOS protocol was simulated in mice, and it had a delayed ovulation than the control group at 12.5 hours after hCG trigger. The suppressed LH level of PPOS group led to the reduced expression of LHCGR on the preovulatory follicles before trigger, and significantly decreased the following progesterone synthesis, blood progesterone level and progesterone-receptor (PGR) expression within 4-6 hours after hCG trigger. Furthermore, the important ovulatory genes regulated by PGR including ADAMTS1, VEGF-A and EDN2 were downregulated in the PPOS group, ultimately delaying the ovulation. Meanwhile, the distribution of ovulation trigger–OPU time intervals with oocyte retrieval rate (>70%) and mature oocyte rate (>80%) in patients using PPOS also indirectly indicate the delayed ovulation. This research provides the crucial evidence for patients using PPOS when arranging the OPU time interval.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A delayed ovulation of Progestin-Primed Ovarian Stimulation (PPOS) by down-regulating the LHCGR/PGR pathway

Xie

Guo

Shen

et al. 2022

Preprint

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“…Thirdly, the sample size was small, especially in the CC + hMG group. Fourth, the interval between ovulation triggering and oocyte retrieval was not analyzed in the study, but it was crucial to preventing ovulation before the retrieval while ensuring proper maturity of oocytes, especially when there was a premature LH surge [ 43 , 44 ]. Caution is needed when interpreting the results, and future randomized controlled trials with a larger sample size are called for.…”

Section: Discussionmentioning

confidence: 99%

Preventing Growth Stagnation and Premature LH Surge Are the Keys to Obtaining a Viable Embryo in Monofollicular IVF Cycles: A Retrospective Cohort Study

Guo

Zhu

et al. 2022

JCM

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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.

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“…injections of hCG (1000–5000 IU). Transvaginal ultrasound-guided oocyte retrieval was conducted 34–36 h after the trigger in the PPOS strategy ( Kuang et al , 2015 ; Wang et al , 2018 ; Yu et al , 2018 ; Shen et al , 2019 ) and at 32–36 h in the LPS protocol ( Kuang et al , 2014 ). All follicles with a diameter greater than 10 mm were aspirated.…”

Section: Methodsmentioning

confidence: 99%

The cumulative live birth rates of 18 593 women with progestin-primed ovarian stimulation-related protocols and frozen-thawed transfer cycles

Nie,

Guo,

Shen

et al. 2023

Human Reproduction Open

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STUDY QUESTION What are the odds of achieving pregnancy when adopting progestin-primed ovarian stimulation (PPOS)-related protocols combined with repetitive frozen–thawed transfer (FET) cycles in patients with different clinical characteristics? SUMMARY ANSWER The cumulative live birth rates (CLBRs) of women undergoing different PPOS-related protocols can be significantly and consistently enhanced within six FET cycles when the female age is < 40 years (or even <45 years) and when >5 oocytes are retrieved, regardless of antral follicle count (AFC). WHAT IS KNOWN ALREADY There have been numerous studies on the live birth rate of the first FET cycle in patients with PPOS-related protocols. These studies have focused mainly on comparing pregnancy outcomes with those of other stimulation protocols. However, owing to the unique features of the PPOS-related strategy, such as its flexible timing of oocyte retrieval and repeated transfer of frozen embryos, studies using the CLBR as an overall indicator of success and investigating which types of patients would benefit from this protocol are lacking. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included 18,593 women who underwent PPOS-related protocols (dydrogesterone + hMG, medroxyprogesterone acetate + hMG, micronized progesterone + hMG treatment, and luteal-phase ovarian stimulation protocol) from 1 March 2011 to 31 September 2022 in our centre. PARTICIPANTS/MATERIALS, SETTING, METHODS The population was categorized by female age, number of oocytes retrieved, and AFC in the analysis of CLBR within six FET cycles. The age groups (groups 1-5, respectively) were <30, 30-34, 35-39, 40-44, and ≥45 years. The number of oocytes retrieved was grouped as 1-5, 6-10, 11-15, 16-20, and >20. AFC was grouped as < 5, 5-10, 11-15, and >15. The Kaplan–Meier analysis (optimistic method), which hypothesized that patients who did not continue treatment had the same chance of achieving a live birth as those who continued, and the competing risk method (conservative method) which hypothesized they had no chance of achieving a live birth, were applied. In further analyses, the Cox model and Fine–Gray model were adopted: the former corresponds to the optimistic scenario, and the latter corresponds to the pessimistic scenario. MAIN RESULTS AND THE ROLE OF CHANCE CLBR had a declining trend with female age over six FET cycles (groups 1-5, respectively: optimistic: 96.9%, 96.6%, 91.4%, 67.3%, and 11.7%; conservative: 87.3%, 85.0%, 74.0%, 41.3%, and 7.5%), requiring more FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 4 and >6 cycles; conservative: 2, 2, 2, > 6 and > 6 cycles). CLBR showed an increasing trend with the number of oocytes retrieved (groups 1-5, respectively: optimistic: 93.8%, 94.3%, 95.8%, 96.0%, and 95.6%; conservative: 66.2%, 78.3%, 85.6%, 88.9%, and 91.0%). All groups needed the same number of FET cycles to achieve a success rate of at least 50% (groups 1-5, respectively: optimistic: 2, 2, 2, 2 and 2 cycles; conservative: 2, 2, 2, 2 and 2 cycles). Furthermore, the CLBR within six FET cycles had an increasing trend with AFC number (groups 1-4, respectively: optimistic: 89.2%, 94.8%, 95.9%, and 96.3%; conservative: 67.4%, 78.2%, 83.9%, and 88.1%), with all four groups achieving a success rate of at least 50% by the second FET cycle. LIMITATIONS, REASONS FOR CAUTION The current research is limited by its retrospective design and single-centre nature, which may restrict the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS This work describes two models (the Kaplan–Meier analysis and the competing risk method) to evaluate the clinical outcome of patients using PPOS-related protocols, which are especially useful for patients of advanced age or those with diminished ovarian reserve. Our findings encourage patients below 45 years old, especially younger than 40 years, and patients with lower AFCs and fewer retrieved oocytes to try this new protocol. Moreover, this study demonstrates the degree of improvement in the CLBR within six FET cycles for patients with different clinical characteristics, providing a valuable point of reference to determine whether to continue ART after a transfer failure. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by grants from the National Natural Science Foundation of China (grant number: 82071603 to L.W., 82001502 to Y. Liu). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

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Optimal Ovulation Trigger–Oocyte Pickup Interval in Progestin-Primed Ovarian Stimulation Protocol: A Retrospective Study Using Propensity Score Matching

Cited by 7 publications

References 31 publications

A delayed ovulation of Progestin-Primed Ovarian Stimulation (PPOS) by down-regulating the LHCGR/PGR pathway

A delayed ovulation of Progestin-Primed Ovarian Stimulation (PPOS) by down-regulating the LHCGR/PGR pathway

Preventing Growth Stagnation and Premature LH Surge Are the Keys to Obtaining a Viable Embryo in Monofollicular IVF Cycles: A Retrospective Cohort Study

The cumulative live birth rates of 18 593 women with progestin-primed ovarian stimulation-related protocols and frozen-thawed transfer cycles

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