scholarly journals Luteal phase ovarian stimulation following oocyte retrieval: is it helpful for poor responders?

Author(s):  
John Zhang
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Biscaro ◽  
A R Lorenzon ◽  
E L Motta ◽  
C Gomes

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


2019 ◽  
Vol 32 (1) ◽  
pp. 25
Author(s):  
Mariana Carlos Alves ◽  
Andreia Leitão Marques ◽  
Helena Barros Leite ◽  
Ana Paula Sousa ◽  
Teresa Almeida-Santos

Introduction: Medically assisted reproduction in natural cycle has been investigated, especially in women with poor response to conventional ovarian stimulation, with endometrial receptivity improvement, lower cost and possibility of successive cycles. The disadvantages are: lower profitability per treatment cycle and higher cancellation rate. The aim of this study was to determine the rate of clinical pregnancy in infertile women subjected to medically assisted reproduction in natural cycle.Material and Methods: Retrospective study of 149 medically assisted reproduction without ovarian stimulation of 50 infertile women, between January/2011 and October/2014.Results: The mean age of women undergoing medically assisted reproduction in natural cycle was 36.1 years. Approximately half (46.0%) of the cycles were performed in poor responders. On the day of ovulation trigger, the mean diameter of the follicle was 17.5 mm. Twenty-three cycles (15.4%) were canceled prior to ovulation trigger. In 8 cycles (5.3%), ovulation occurred between ovulation trigger and oocyte retrieval. In the majority of cycles (n = 118; 79.2%) oocyte retrieval was executed, a medically assisted reproduction technique was performed in 71 (47.6%), mostly intracytoplasmic injection. The overall fertilization rate was 77.5%. In 40 cycles (26.8%) there was embryo transfer. The implantation rate and the clinical pregnancy rate by embryo transfer was 35.0% and 25.0%, respectively. Most pregnancies occurred in poor responders, according to Bologna criteria.Discussion: Although the pregnancy rate per cycle started was 6.7%, the rate of clinical pregnancy per embryo transfer is quite satisfactory, being a group of women with unfavorable responses in previous treatments. The relatively high rates of cycle cancellation are mitigated by the greater simplicity and lower cost of these cycles.Conclusion: The results obtained in this study demonstrate that Medically Assisted Reproduction in natural cycle may be an alternative treatment for ovarian stimulation in patients with poor prognosis, whose only alternative would be oocyte donation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Biscaro ◽  
A R Lorenzon ◽  
E L Motta ◽  
C Gomes

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


2020 ◽  
Author(s):  
Li-Te Lin ◽  
Ju-Yueh Li ◽  
Kuan-Hao Tsui ◽  
Chia-Jung Li ◽  
Peng-Hui Wang ◽  
...  

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.


Medicina ◽  
2019 ◽  
Vol 55 (3) ◽  
pp. 68 ◽  
Author(s):  
Konstantinos Sfakianoudis ◽  
Mara Simopoulou ◽  
Evangelos Maziotis ◽  
Polina Giannelou ◽  
Petroula Tsioulou ◽  
...  

Background: Emergence of Luteal Phase Oocyte Retrieval (LuPOR) may revolutionize the practice regarding the time-sensitive nature of poor responders ascertaining a higher number of oocytes, in a shorter amount of time. This may be especially important in view of employing the approach of natural cycles for Poor Responders. We suggest the acronym LuPOR describing the clinical practice of luteal phase oocyte retrieval. The aim of the study is to offer insight regarding the identity of LuPOR, and highlight how this practice may improve management of the special subgroup of poor responders. Materials and Methods: The present retrospective observational clinical study includes the collection and statistical analysis of data from 136 poor responders who underwent follicular oocyte retrieval (FoPOR) and subsequent LuPOR in natural cycles, during their In Vitro Fertilization (IVF) treatment, from the time period of 2015 to 2018. All 136 participants were diagnosed with poor ovarian reserve (POR) according to Bologna criteria. The 272 cycles were categorized as follows: 136 natural cycles with only FoPORs (Control Group) and 136 natural cycles including both FoPORs and LuPORs. Results: Our primary results indicate no statistically significant differences with regards to the mean number of oocytes, the maturation status, and fertilization rate between FoPOR and LuPOR in natural cycles. Secondarily, we demonstrate a statistically significant higher yield of oocytes (2.50 ± 0.78 vs. 1.25 ± 0.53), better oocyte maturity status (1.93 ± 0.69 vs. 0.95 ± 0.59) and higher fertilization rate (1.31 ± 0.87 vs. 0.61 ± 0.60) in natural cycles including both FoPOR and LuPOR, when compared to cycles including only FoPOR. Conclusion: Our study may contribute towards the establishment of an efficient poor responders’ management through the natural cycle approach, paving a novel clinical practice and ascertaining the opportunity to employ oocytes and embryos originating from a luteal phase follicular wave.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Sfakianoudis ◽  
D Galatis ◽  
E Maziotis ◽  
A Pantou ◽  
P Giannelou ◽  
...  

Abstract Study question Can successful implementation of luteal phase oocyte retrieval (LuPOR) following conventional follicular phase oocyte retrieval (FoPOR) be predicted for poor ovarian response (POR) patients? Summary answer Antral follicle count (AFC), number of small follicles recorded in FoPOR, and estradiol (E2) levels on FoPOR and LuPOR trigger days, predict successful LuPOR application. What is known already A second follicular wave in the same menstrual cycle was first observed in domestic animals such as horses and cattle and thenceforth in women. The second follicular wave has been introduced as an encouraging means towards optimizing the context of in vitro fertilization (IVF) success rates for infertile women and especially for POR patients. Double ovarian stimulation coupled with two oocyte retrievals in the same menstrual cycle has been proposed, and encouraging results have been reported. However, the high heterogeneity characterizing POR patients dictates that studies should focus on factors indicating efficient LuPOR application. Study design, size, duration This retrospective observational study included 1688 women diagnosed with POR, undergoing natural IVF cycles between 2012–2020 including two oocyte retrievals in the same menstrual cycle. Patients’ age, body mass index (BMI), number of previous POR incidences, basal hormonal levels, AFC, E2 evaluated on both trigger days and number of small follicles (8–13 mm) were evaluated on their predictive power regarding retrieval of at least one MII oocyte following LuPOR, being regarded as successful LuPOR implementation. Participants/materials, setting, methods A diagnosis of POR according to Bologna criteria served as the inclusion criterion for this single center study. All other infertility etiologies were excluded. Patient dataset was stratified according to age in quantiles. A random 20% of each quantile was employed to validate the model. The remaining 80% was employed to develop this model. The predictive value was determined employing the Area Under the Curve (AUC) of the Receiver Operating Characteristics, employing Youden’s index. Main results and the role of chance Patients’ age, BMI, number of previous failed IVF attempts, basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin and progesterone failed to be predictive of a successful LuPOR as the AUC was below 0.6. AFC with a threshold value of 4.47, was found to be predictive of an effective LuPOR with an AUC of 0.86, sensitivity 0.8, specificity 0.75, and accuracy 0.79. E2 levels evaluated on the FoPOR trigger day, with a threshold value of 232.66 pg/ml, were similarly predictive of an effective LuPOR presenting with an AUC 0.86, specificity 0.75, sensitivity 0.86 and accuracy 0.82. Similarly, E2 evaluated on the LuPOR trigger day, with a threshold value of 200.89 pg/ml, presented with an AUC 0.89, specificity 0.85, sensitivity 0.95 and accuracy 0.92. The number of small follicles during FoPOR also appeared to be predictive of the presence of at least one MII oocyte during LuPOR, with a threshold value of 2.94. The AUC was 0.82, specificity 0.75, sensitivity 0.76 and accuracy 0.75. When combining the above characteristics into a single predictive model the AUC was 0.88, specificity 0.73, sensitivity 0.94 and accuracy 0.89. The positive and negative predictive value of the model were 93.5% and 46.8%, respectively. Limitations, reasons for caution Employment of natural cycles may present as a limitation when examining the value of this study, as the cut-off values reported herein may be altered when stimulation is employed. Since internal validation may be confounded by the fact that this was a single center study, external validation is required. Wider implications of the findings: The clinical end-point of this study reporting back to the practitioner, is the development of a predictive model identifying the optimal POR population for whom LuPOR practice is valuable. The high positive predictive value of this model may assist clinicians in identifying poor responders who will benefit from this approach. Trial registration number Not applicable


Sign in / Sign up

Export Citation Format

Share Document