scholarly journals Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study

2021 ◽  
Vol 18 (7) ◽  
pp. 1600-1608
Author(s):  
Yu-Chen Chen ◽  
Ju-Yueh Li ◽  
Chia-Jung Li ◽  
Kuan-Hao Tsui ◽  
Peng-Hui Wang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Cumulus Cell ◽  
Follicular Phase ◽  
Genes Expression ◽  
Luteal Phase Ovarian Stimulation

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

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

Luteal phase ovarian stimulation versus follicular phase ovarian stimulation results in different human cumulus cells gene expression: a pilot study

2020 ◽  
Author(s):  
Li-Te Lin ◽  
Ju-Yueh Li ◽  
Kuan-Hao Tsui ◽  
Chia-Jung Li ◽  
Peng-Hui Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Cumulus Cells ◽  
Follicular Phase ◽  
Basic Characteristics ◽  
The Impact ◽  
Luteal Phase Ovarian Stimulation

Abstract OBJECTIVE: Physiologic elevated levels of progesterone in luteal phase can impede early-onset LH surge. However, the impact of high levels of progesterone on the oocyte or cumulus cells (CCs) remains indistinct. Therefore, the aim of study was to investigate the CCs gene expression between luteal phase ovarian stimulation (LPOS) and follicular phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing in vitro fertilization (IVF) cycles. MATERIALS AND METHODS: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who conformed Bologna criteria and underwent IVF cycles were enrolled. 15 PORs were allocated to the LPOS group and 21 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics and pregnancy outcomes were compared between the two groups. Moreover, CCs genes regarding inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative-phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR between the two groups. RESULTS: Basic characteristics and IVF outcomes were similar between the two groups except significantly high progesterone level in the LPOS group. The mRNA expression of CXCL1 and PTGES were significantly lower in the LPOS group than in the FPOS group ( p < 0.05). The LPOS group had significantly lower mRNA expression of NDUFB7 and NDUFA4L2 than the FPOS group ( p < 0.05). DAPK3 and BCL6B mRNA expression were significantly higher in the LPOS group compared to FPOS group ( p < 0.05). Increased expression of PCK1 and decreased expression of LDHC were observed in the LPOS group compared to the FPOS group. ( p < 0.05). CONCLUSIONS: Compared to the FPOS, the LPOS seemed to reduce favorable inflammation and mitochondrial function, and induce apoptosis and abnormal glucose metabolism in CCs.

The euploid blastocysts obtained after luteal phase stimulation show the same clinical, obstetric and perinatal outcomes as follicular phase stimulation-derived ones: a multicenter study

2020 ◽  
Vol 35 (11) ◽  
pp. 2598-2608
Author(s):  
Alberto Vaiarelli ◽  
Danilo Cimadomo ◽  
Erminia Alviggi ◽  
Anna Sansone ◽  
Elisabetta Trabucco ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Live Birth ◽  
Multicenter Study ◽  
Gestational Age ◽  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Perinatal Outcomes ◽  
Follicular Phase ◽  
Blastocyst Transfer ◽  
Large For Gestational Age

Abstract STUDY QUESTION Are the reproductive outcomes (clinical, obstetric and perinatal) different between follicular phase stimulation (FPS)- and luteal phase stimulation (LPS)-derived euploid blastocysts? SUMMARY ANSWER No difference was observed between FPS- and LPS-derived euploid blastocysts after vitrified-warmed single embryo transfer (SET). WHAT IS KNOWN ALREADY Technical improvements in IVF allow the implementation non-conventional controlled ovarian stimulation (COS) protocols for oncologic and poor prognosis patients. One of these protocols begins LPS 5 days after FPS is ended (DuoStim). Although, several studies have reported similar embryological outcomes (e.g. fertilization, blastulation, euploidy) between FPS- and LPS-derived cohort of oocytes, information on the reproductive (clinical, obstetric and perinatal) outcomes of LPS-derived blastocysts is limited to small and retrospective studies. STUDY DESIGN, SIZE, DURATION Multicenter study conducted between October 2015 and March 2019 including all vitrified-warmed euploid single blastocyst transfers after DuoStim. Only first transfers of good quality blastocysts (≥BB according to Gardner and Schoolcraft’s classification) were included. If euploid blastocysts obtained after both FPS and LPS were available the embryo to transfer was chosen blindly. The primary outcome was the live birth rate (LBR) per vitrified-warmed single euploid blastocyst transfer in the two groups. To achieve 80% power (α = 0.05) to rule-out a 15% difference in the LBR, a total of 366 first transfers were required. Every other clinical, as well as obstetric and perinatal outcomes, were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS Throughout the study period, 827 patients concluded a DuoStim cycle and among them, 339 did not identify any transferable blastocyst, 145 had an euploid blastocyst after FPS, 186 after LPS and 157 after both FPS and LPS. Fifty transfers of poor quality euploid blastocysts were excluded and 49 patients did not undergo an embryo transfer during the study period. Thus, 389 patients had a vitrified-warmed SET of a good quality euploid blastocyst (182 after FPS and 207 after LPS). For 126 cases (32%) where both FPS- and LPS-derived good quality blastocysts were available, the embryo transferred was chosen blindly with a ‘True Random Number Generator’ function where ‘0’ stood for FPS-derived euploid blastocysts and ‘1’ for LPS-derived ones (n = 70 and 56, respectively) on the website random.org. All embryos were obtained with the same ovarian stimulation protocol in FPS and LPS (GnRH antagonist protocol with fixed dose of rec-FSH plus rec-LH and GnRH-agonist trigger), culture conditions (continuous culture in a humidified atmosphere with 37°C, 6% CO2 and 5% O2) and laboratory protocols (ICSI, trophectoderm biopsy in Day 5–7 without assisted hatching in Day 3, vitrification and comprehensive chromosome testing). The women whose embryos were included had similar age (FPS: 38.5 ± 3.1 and LPS: 38.5 ± 3.2 years), prevalence of male factor, antral follicle count, basal hormonal characteristics, main cause of infertility and previous reproductive history (i.e. previous live births, miscarriages and implantation failures) whether the embryo came from FPS or LPS. All transfers were conducted after warming in an artificial cycle. The blastocysts transferred after FPS and LPS were similar in terms of day of full-development and morphological quality. MAIN RESULTS AND THE ROLE OF CHANCE The positive pregnancy test rates for FPS- and LPS-derived euploid blastocysts were 57% and 62%, biochemical pregnancy loss rates were 10% and 8%, miscarriage rates were 15% and 14% and LBRs were 44% (n = 80/182, 95% CI 37–51%) and 49% (n = 102/207, 95% CI 42–56%; P = 0.3), respectively. The overall odds ratio for live birth (LPS vs FPS (reference)) adjusted for day of blastocyst development and quality, was 1.3, 95% CI 0.8–2.0, P = 0.2. Among patients with euploid blastocysts obtained following both FPS and LPS, the LBRs were also similar (53% (n = 37/70, 95% CI 41–65%) and 48% (n = 27/56, 95% CI 35–62%) respectively; P = 0.7). Gestational issues were experienced by 7.5% of pregnant women after FPS- and 10% of women following LPS-derived euploid single blastocyst transfer. Perinatal issues were reported in 5% and 0% of the FPS- and LPS-derived newborns, respectively. The gestational weeks and birthweight were similar in the two groups. A 5% pre-term delivery rate was reported in both groups. A low birthweight was registered in 2.5% and 5% of the newborns, while 4% and 7% showed high birthweight, in FPS- and LPS-derived euploid blastocyst, respectively. Encompassing the 81 FPS-derived newborns, a total of 9% were small and 11% large for gestational age. Among the 102 LPS-derived newborns, 8% were small and 6% large for gestational age. No significant difference was reported for all these comparisons. LIMITATIONS, REASONS FOR CAUTION The LPS-derived blastocysts were all obtained after FPS in a DuoStim protocol. Therefore, studies are required with LPS-only, late-FPS and random start approaches. The study is powered to assess differences in the LBR per embryo transfer, therefore obstetric and perinatal outcomes should be considered observational. Although prospective, the study was not registered. WIDER IMPLICATIONS OF THE FINDINGS This study represents a further backing of the safety of non-conventional COS protocols. Therefore, LPS after FPS (DuoStim protocol) is confirmed a feasible and efficient approach also from clinical, obstetric and perinatal perspectives, targeted at patients who need to reach the transfer of an euploid blastocyst in the shortest timeframe possible due to reasons such as cancer, advanced maternal age and/or reduced ovarian reserve and poor ovarian response. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Is 5HT1A Receptor Subsensitivity a Trait Marker for Late Luteal Phase Dysphoric Disorder? A Pilot Study

1993 ◽  
Vol 38 (10) ◽  
pp. 662-664 ◽  
Author(s):  
Lakshmi N. Yatham
Keyword(s):  
Pilot Study ◽  
Luteal Phase ◽  
Follicular Phase ◽  
Healthy Controls ◽  
5Ht1a Receptor ◽  
Trait Marker ◽  
Late Luteal Phase ◽  
State Marker

Prolactin responses to buspirone challenges were examined in seven women with late luteal phase dysphoric disorder and the same number of healthy controls. The responses were found to be blunted during the follicular phase in the women with LLPDD suggesting that 5-HT1A receptor subsensitivity is perhaps a trait rather than a state marker for LLPDD.

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