Faculty Opinions recommendation of Ovarian follicular waves during the menstrual cycle: physiologic insights into novel approaches for ovarian stimulation.

2020 ◽  
Author(s):  
Rosemarie Heyn
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Follicular Waves ◽  
Novel Approaches

scholarly journals Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Sophie Fischer ◽  
Rainald Ehrig ◽  
Stefan Schäfer ◽  
Enrico Tronci ◽  
Toni Mancini ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Time Course ◽  
Scientific Evidence ◽  
Coupled Model ◽  
Continuous Growth ◽  
Time Points ◽  
Follicular Waves ◽  
Normal Menstrual Cycle

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

P–656 Examination of the clinical significance of the two-step ovulation induction method (DuoStim)

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Anzawa ◽  
T Nagasaki ◽  
Y Kasagi ◽  
C Kato ◽  
Y Omi ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Ovulation Induction ◽  
Statistical Significance ◽  
Hormone Replacement ◽  
Arrival Rate ◽  
Clinical Pregnancy ◽  
Freeze Thaw ◽  
Egg Maturation ◽  
Significant Difference

Abstract Study question Do culture results of eggs obtained by double stimulation (DuoStim), where eggs are collected twice in one cycle, differ from a conventional fertility drug method? Summary answer The culture results of eggs acquired via the DuoStim cycle versus those acquired via a widely used conventional fertility drug method did not differ significantly. What is known already For patients with reduced ovarian reserve, the random start method, in which ovarian stimulation can start at any time during the menstrual cycle, is being used. As the pituitary gland is suppressed by progesterone during the luteal phase, endogenous luteinizing hormone surges are less likely to occur and ovulation is more easily avoidable. Previous reports showed that ovarian stimulation during the follicular and luteal phases of the same menstrual cycle resulted in similar blastocyst formation rates with normal chromosome numbers, which seems to be time-consuming. The DuoStim method is considered useful in cases in which time is at a premium. Study design, size, duration Between June 2019–December 2020, 562 egg collection cycles were performed in women ≥36 years. Ovulation cycles were evaluated in the conventional ovulation induction cycle (Co) group and DuoStim cycle (DS) group (subclassified into D1 group [first egg collection in cycle] and D2 group [second egg collection]. Post-insemination culture results were evaluated. Participants/materials, setting, methods Participants were women ≥36 years. Infusion method was IVF, and blastocysts of Gardner classification 3BB or higher were designated as good blastocysts, and blastocysts of 3AA or higher were designated as the best blastocysts. Confirmation of the fetal sac was defined as clinical pregnancy for the single freeze-thaw blastocyst transplant cycle. Chi-square and t-tests were used for statistical analysis. P ≤ 0.05 indicated statistical significance. Main results and the role of chance The average number of eggs acquired per cycle was 6.9 in the Co group and 3.5 in the DS group, and the egg maturation rate was 88.0% in the Co group and 95.7% in the DS group, which showed significant differences. The 2PN rate, blastocyst arrival rate, and Day 5 good blastocyst arrival rate in the obtained mature eggs were 66.5%, 66.5%, and 38.3% in the Co group and 70.9%, 70.5%, and 34.4% in the DS group and were not significantly different. Similarly, when a comparative study was conducted between the D1 group and D2 group, rates were 67.5%, 69.0%, and 31.0% in the D1 group and 74.4%, 71.9%, and 37.5% in the D2 group, with no significant difference noted. Rates of clinical pregnancy and post-transplantation miscarriage were 41.1% and 17.8% in the Co group and 16.6% and 0% in the DS group, respectively, with no significant difference, although rates in the Co group tended to be better. Limitations, reasons for caution The fertilization method was evaluated only by IVF. The transplantation method was freeze-thaw embryo transfer by hormone replacement cycle, and the target age was 36 years or older. Wider implications of the findings: DuoStim, which increases the number of acquired eggs, is useful when eggs must be collected as soon as possible. Regarding the clinical pregnancy rate after transplantation, better results were obtained for eggs acquired by the conventional fertility method, but it was necessary to repeat the number of attempts. Trial registration number Not applicable

P–643 Is Euploid blastocyst number higher in luteal versus follicular phase? A case-control study of IVF outcomes of follicular versus luteal phase ovarian stimulation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Biscaro ◽  
A R Lorenzon ◽  
E L Motta ◽  
C Gomes
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Case Control Study ◽  
Case Control ◽  
Follicular Phase ◽  
Menstrual Cycles ◽  
Ivf Outcomes ◽  
Control Study ◽  
Luteal Phase Ovarian Stimulation

Abstract Study question Is there a difference between IVF outcomes in patients undergoing follicular versus luteal phase ovarian stimulation in different menstrual cycles? Summary answer Number of euploid blastocyst were higher in luteal phase ovarian stimulation IVF cycles. All other outcomes were similar between follicular and luteal phase IVF cycles. What is known already It has been published that human beings can have two or three follicular recruitment waves as observed in animals studies a long time ago. From these findings, several recent studies showed that two egg retrievals at the same menstrual cycle, named as Duo Stim, optimize time and IVF outcomes in women with low ovarian reserve due to more eggs retrieved in a shorter period with consequently higher probability of having good embryos to transfer. However, there is no knowledge about diferences concerning IVF outcomes between folicular and luteal ovarian stimulation, performed at the same women in different menstrual cycles. Study design, size, duration Retrospective, case-control study in a single IVF center. One-hundred-two patients who had two IVF treatments – the first cycle initiating ovarian stimulation at follicular phase (FPS) and the second cycle initiating after a spontaneous ovulation at luteal phase (LPS) – in different menstrual cycles (until 6 months apart) between 2014 and 2020, were included. Statistical analysis was performed with Mann-Whitney test and was considered significant when p ≤ 0.05. Data is represented as mean±SD. Participants/materials, setting, methods Patients underwent two IVF treatments in different menstrual cycles; the FPS IVF treatment was initiating at D2/D3 of menstrual cycle and the LPS treatment started three or four days after spontaneous ovulation, if at least 4 antral follicles were detected. Both IVF treatments were performed with and antagonist protocol and freeze all strategy. The majority of patients presents low ovarian reserve/Ovarian age as primary infertility factor (84.3%). Main results and the role of chance Patient’s mean age was 39.30±3.15 years, BMI (22.66±3.16) and AMH levels (0.85±0.85 ng/mL). Comparison of hormonal levels at the beginning of ovarian stimulation showed differences for FPS vs LPS, as expected: E2 (39.69±31,10 pg/mL vs 177.33±214.26 pg/mL,p< 0.0001) and P4 (0.76±2.47ng/mL vs 3,00±5.00 ng/mL,p< 0.0001). However, E2 and P4 at the day of oocyte maturation trigger were not different between FPS and LPS (1355.24±895.73 pg/mL vs 1133.14±973.01 ng/mL,p=0.0883 and 1.12±1.49 ng/mL vs 2.94±6.51,p=0.0972 respectively). There was no difference for total dose of gonadotrofins (FPS 2786.43±1102.39.01UI vs LPS 2824.12±1188.87UI, p = 0,8578), FSH (FPS 9.50±4.98 vs LPS 11.90±12.99,p=0.7502) and AFC (FPS 7.13±4.25 vs LPS 6.42±4.65,p=0,0944). From 102 patients that started ovarian stimulation, 78 had 1 or more oocyte collect in FPS group and 75 in LPS group: OPU (FPS 4.78±4.93 vs LPS 4.65±5.54,p=0.7889), number of MII (FPS 3.21±3.52 vs LPS 3.40±4.53,p=0.7889). From those, 52 patients performed ICSI in both cycles; fertilization rate 64.9%±28.6% for FPS vs 62.1%±32.4% for LPS,p=0.7899) and blastocyst formation 2.15±2.15 for FPS vs 2.54±2.35,p=0.3496). Data from 25 patients who had embryo biopsy for PGT-A showed similar number of blastocyst biopsed (2.12±1.72 FPS vs 2.48±1.71 LPS,p=0.3101) and a statistically significant difference regarding number of euploid blastocyst (0,20±0,41 FPS vs 0,96±0,93 LPS,p=0,0008). Limitations, reasons for caution This is a retrospective study in a limited number of patients. Therefore, it is not possible to make a definitive conclusion that LPS proportionate higher number of euploid than FPS. More studies are necessary to investigate not only IVF outcomes but also the impact on pregnancy rates. Wider implications of the findings: In our study, LPS protocol after spontaneous ovulation, presents similar IVF outcomes compared to routinely FPS protocol. Intriguingly, the number of euploid blastocyst was significant higher in LPS, which may be further investigated. In this way, LPS is another option of IVF treatment, and may optimize time and treatment results. Trial registration number Not applicable

O-111 The DuoStim strategy shortens the time to obtain an euploid embryo in poor prognosis patients: a non-inferiority, randomized controlled trial

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Cerrillo Martínez ◽  
G. N Cecchino ◽  
M Cruz ◽  
M Toribio ◽  
M J García Rubio ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Poor Prognosis ◽  
Controlled Trial ◽  
Ovarian Response ◽  
Randomized Controlled ◽  
The Mean ◽  
Euploid Embryo

Abstract Study question Is there any difference in the time to obtain euploid embryos from poor prognosis patients who performed two conventional cycles versus double stimulation (DuoStim) in the same cycle? Summary answer DuoStim showed similar ovarian response and in vitro fertilization (IVF) laboratory outcomes while shortening the time to obtain an euploid embryo in poor prognosis patients. What is known already Several waves of cyclic development of antral follicles within the same menstrual cycle have been demonstrated. Likewise, it has been shown that oocytes obtained from luteal phase ovarian stimulation (OS) have similar competence than those obtained in the follicular phase OS. Often, some patients require sequential OS in order to obtain more oocytes and increase their chances to reach embryo transfer. Thus, the DuoStim strategy could be an attractive alternative to reduce the time-to-pregnancy. However, prospective data and randomized trials that validate this strategy are lacking. Study design, size, duration We conducted a prospective, randomized controlled trial at our institution from[MCM1] [JAGV2] January 2017 to December 2020. A total of 80 poor prognosis patients aged over 38 years undergoing PGT-A were enrolled in two groups: 39 patients did two OS in consecutive cycles (control) whereas 41 women underwent two OS in the same menstrual cycle (DuoStim). Participants/materials, setting, methods Poor prognosis was defined as suboptimal responders. The primary outcome was the time needed to obtain an euploid embryo. The secondary outcomes were duration of stimulation, dose of gonadotropins, oocyte maturity rate, fertilization and blastocyst formation rates. Variables were expressed as mean ± standard deviation. Statistical analyses was performed by ANOVA and Chi-square tests, as appropriate. Differences were considered significant when p-value < 0.05. Main results and the role of chance The patients’ baseline characteristics were similar between groups. We did not find any difference in the mean days of stimulation between the control and the DuoStim group (21.3 ± 1.6 vs. 23 ± 1.4, p = 0.105), nor in the amount of gonadotropin required (4005 ± 450 vs. 4245 ± 430, p = 0.43), number of MII oocyte (8.7 ± 1.8 vs. 6.8 ± 1.7, p = 0.159), blastocyst rate (51.4% vs. 34.8%, p = 0.113) and the number of euploid embryos (0.8 ± 0.4 vs. 0.6 ± 0.4, p = 0.45). However, there was a significant difference in the average number of days until reaching an euploid blastocyst, favoring the DuoStim group (44.1 ± 2 vs. 23.3 ± 2.8, p < 0.001). Comparing the follicular versus the luteal phase within the DuoStim group, the only difference detected concerns to the mean days of stimulation (10.3 ± 0.8 vs. 12.7 ± 0.9, p < 0.001). We also observed a trend towards a higher fertilization (38.1% vs. 61.8%, p = 0.02) and blastulation rate (23% vs. 53%, p = 0.03) in the luteal phase of the DuoStim cycle. Limitations, reasons for caution The major limitation is related to the limited sample size, as it limits our power analysis (70%). On the other hand, it is one of the first randomized prospective pilot trial that compared the efficiency of performing two consecutive ovarian stimulation in different menstrual cycles with the DuoStim strategy. Wider implications of the findings This study clearly showed that the DuoStim protocol is not inferior to the conventional stimulation in terms of ovarian response and laboratory outcomes. Moreover, the DuoStim reduces the time to obtain an euploid embryo in poor prognosis patients, which is of great clinical utility. Trial registration number NCT03291821

P-643 Pre-selected for an award: Is Euploid blastocyst number higher in luteal versus follicular phase? A case-control study of IVF outcomes of follicular versus luteal phase ovarian stimulation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Biscaro ◽  
A R Lorenzon ◽  
E L Motta ◽  
C Gomes
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Case Control Study ◽  
Case Control ◽  
Follicular Phase ◽  
Menstrual Cycles ◽  
Ivf Outcomes ◽  
Control Study ◽  
Luteal Phase Ovarian Stimulation

Abstract Study question Is there a difference between IVF outcomes in patients undergoing follicular versus luteal phase ovarian stimulation in different menstrual cycles? Summary answer Number of euploid blastocyst were higher in luteal phase ovarian stimulation IVF cycles. All other outcomes were similar between follicular and luteal phase IVF cycles. What is known already It has been published that human beings can have two or three follicular recruitment waves as observed in animals studies a long time ago. From these findings, several recent studies showed that two egg retrievals at the same menstrual cycle, named as Duo Stim, optimize time and IVF outcomes in women with low ovarian reserve due to more eggs retrieved in a shorter period with consequently higher probability of having good embryos to transfer. However, there is no knowledge about diferences concerning IVF outcomes between folicular and luteal ovarian stimulation, performed at the same women in different menstrual cycles. Study design, size, duration Retrospective, case-control study in a single IVF center. One-hundred-two patients who had two IVF treatments – the first cycle initiating ovarian stimulation at follicular phase (FPS) and the second cycle initiating after a spontaneous ovulation at luteal phase (LPS) – in different menstrual cycles (until 6 months apart) between 2014 and 2020, were included. Statistical analysis was performed with Mann-Whitney test and was considered significant when p ≤ 0.05. Data is represented as mean±SD. Participants/materials, setting, methods Patients underwent two IVF treatments in different menstrual cycles; the FPS IVF treatment was initiating at D2/D3 of menstrual cycle and the LPS treatment started three or four days after spontaneous ovulation, if at least 4 antral follicles were detected. Both IVF treatments were performed with and antagonist protocol and freeze all strategy. The majority of patients presents low ovarian reserve/Ovarian age as primary infertility factor (84.3%). Main results and the role of chance Patient’s mean age was 39.30±3.15 years, BMI (22.66±3.16) and AMH levels (0.85±0.85 ng/mL). Comparison of hormonal levels at the beginning of ovarian stimulation showed differences for FPS vs LPS, as expected: E2 (39.69±31,10 pg/mL vs 177.33±214.26 pg/mL, p < 0.0001) and P4 (0.76±2.47ng/mL vs 3,00±5.00 ng/mL,p < 0.0001). However, E2 and P4 at the day of oocyte maturation trigger were not different between FPS and LPS (1355.24±895.73 pg/mL vs 1133.14±973.01 ng/mL,p = 0.0883 and 1.12±1.49 ng/mL vs 2.94±6.51,p = 0.0972 respectively). There was no difference for total dose of gonadotrofins (FPS 2786.43±1102.39.01UI vs LPS 2824.12±1188.87UI, p = 0,8578), FSH (FPS 9.50±4.98 vs LPS 11.90±12.99, p = 0.7502) and AFC (FPS 7.13±4.25 vs LPS 6.42±4.65,p = 0,0944). From 102 patients that started ovarian stimulation, 78 had 1 or more oocyte collect in FPS group and 75 in LPS group: OPU (FPS 4.78±4.93 vs LPS 4.65±5.54,p = 0.7889), number of MII (FPS 3.21±3.52 vs LPS 3.40±4.53,p = 0.7889). From those, 52 patients performed ICSI in both cycles; fertilization rate 64.9%±28.6% for FPS vs 62.1%±32.4% for LPS,p = 0.7899) and blastocyst formation 2.15±2.15 for FPS vs 2.54±2.35,p = 0.3496). Data from 25 patients who had embryo biopsy for PGT-A showed similar number of blastocyst biopsed (2.12±1.72 FPS vs 2.48±1.71 LPS,p = 0.3101) and a statistically significant difference regarding number of euploid blastocyst (0,20±0,41 FPS vs 0,96±0,93 LPS,p = 0,0008). Limitations, reasons for caution This is a retrospective study in a limited number of patients. Therefore, it is not possible to make a definitive conclusion that LPS proportionate higher number of euploid than FPS. More studies are necessary to investigate not only IVF outcomes but also the impact on pregnancy rates. Wider implications of the findings In our study, LPS protocol after spontaneous ovulation, presents similar IVF outcomes compared to routinely FPS protocol. Intriguingly, the number of euploid blastocyst was significant higher in LPS, which may be further investigated. In this way, LPS is another option of IVF treatment, and may optimize time and treatment results. Trial registration number Not Applicable

scholarly journals Changes in circulating levels and ratios of angiopoietins during pregnancy but not during the menstrual cycle and controlled ovarian stimulation

2010 ◽  
Vol 93 (5) ◽  
pp. 1493-1499 ◽  
Author(s):  
Amanda K. Hurliman ◽  
Leon Speroff ◽  
Richard L. Stouffer ◽  
Phillip E. Patton ◽  
Annette Lee ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Stimulation ◽  
Controlled Ovarian Stimulation ◽  
Circulating Levels

O-112 Outcomes of random-start ovarian stimulation protocols as a possible evidence of the theory of antral follicles continuous recruitment

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Martirosyan ◽  
T Nazarenko ◽  
A Birukova ◽  
I Dmitrieva
Keyword(s):  
Menstrual Cycle ◽  
Ovarian Reserve ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Young Patients ◽  
Serum Levels ◽  
Prospective Clinical Study ◽  
Antral Follicles ◽  
Informed Consent Form ◽  
Significant Difference

Abstract Study question We tried to validate the possibility and efficiency of ovarian stimulation (OS) started on any day of the menstrual cycle, based on a theory of continuous recruitment of antral follicles. Summary answer Formation of a pool of follicles with higher sensitivity to gonadotropic stimulation occurs several times during the menstrual cycle (MC). What is known already According to classical concepts and fundamental positions formulated in the middle of the last century, follicular recruitment occurs only once during the menstrual cycle - in the early follicular phase. Nowadays there is increasing evidence to suggest that there are multiple (two or three) antral follicular waves of recruitment during the MC. Also some researchers state that the process of follicle recruitment is continuous. Study design, size, duration This prospective clinical study was conducted at the V.I. Kulakov NMRC for OG&Pof Russia. The study included female cancer patients seeking retrieval and cryopreservation of oocytes and/or embryos before cancer treatment. 240 patients were selected for the study. The patients were divided into 5 groups depending on the cycle day on the moment when ovarian stimulation was initiated. All patients signed an informed consent form approved by the Ethics Committee. Participants/materials, setting, methods The 1st group consisted of patients who started standart OS from 1 to 5 days of the cycle (n = 65); the 2nd - from 6 to 10 (n = 36), the 3rd - from 11 to 15 (n = 45), the 4th - from 16 to 22 (n = 44), the 5th - from 23 to 28 (n = 50). In the late follicular and luteal phase we performed OS without a pituitary modulator. The comparative analysis included features of oo-, embryogenesis and steroidogenesis. Main results and the role of chance The mean age, BMI and AMH were not different among groups. There were no LH rise or OHSS signs noticed in any groups, despite that OS in late follicular and luteal phase of the MC was performed with no GnRH antagonist addition.There was no statistically significant difference in the duration of stimulation, starting doses, total dose of FSH and HMG. The largest number of oocyte cumulus complexes was obtained in the 5th group (11 (9–21) vs 7 (3,5–15,5) in the 1st group, p = 0,030). The greatest number of mature oocytes was obtained in the 4th and 1st groups. In the 2nd group the largest number of immature oocytes was obtained (37 (9.1%)). A smaller number of mature oocytes (165 (61.8%) vs 492 (72.9%) and 314 (77.5%), p = 0.001) was obtained in group 2 (compared with the 1st and the 4th groups), when stimulation was started in the presence of a dominant follicle . These periods coincided with higher estradiol and lower FSH serum levels. Based on our data the optimal moment for effective OS initiation starts with the decrease in serum estradiol which is approximately 48 hours before the menstrual bleeding. Limitations, reasons for caution The presented results could be applied mainly to young patients with high and normal ovarian reserve, who were in the main study group. In patients with low ovarian reserve, short menstrual cycle and early ovulation an issue of favorable time points for the initiation of OS should be resolved individually. Wider implications of the findings The data collected during our research could possibly contribute to future personification of OS protocols. Tailoring the ovarian stimulation protocols to the needs of the patients could decrease time needed for completing the protocol without affecting oocyte yield or their maturity. Trial registration number none

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