scholarly journals Can ovarian double-stimulation in the same menstrual cycle improve IVF outcomes?

2017 ◽  
Vol 21 (3) ◽  
Author(s):  
Maria Cecília de Almeida Cardoso ◽  
Alessandra Evangelista ◽  
Cássio Sartório ◽  
George Vaz ◽  
Caio Luis Vieira Werneck ◽  
...  
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 ◽  
Vol 41 (3) ◽  
pp. 518-526
Author(s):  
Nona Mishieva ◽  
Bella Martazanova ◽  
Khava Bogatyreva ◽  
Anna Korolkova ◽  
Anastasia Kirillova ◽  
...  

2020 ◽  
Vol 26 (6) ◽  
pp. 904-928 ◽  
Author(s):  
Johnny S Younis ◽  
Rula Iskander ◽  
Bart C J M Fauser ◽  
Ido Izhaki

Abstract BACKGROUND Regular menstrual cycling during the reproductive years is an indicator of spontaneous ovulation but sometimes falsely perceived as an indicator of preserved fertility. In contrast, menstrual cycle shortening, a physiologic occurrence preceding the menopausal transition, is not usually perceived as an indicator of decreased ovarian reserve in the general population. OBJECTIVE AND RATIONALE The individual decrease in menstrual cycle length (MCL) might represent a sensitive biomarker of diminishing ovarian reserve. The aim of this systematic review and meta-analysis is to examine the possible association between MCL in regularly cycling women (21–35 days) and ovarian reserve tests (ORT), fecundability in natural cycles and IVF outcomes. SEARCH METHODS An electronic database search employing PubMed, Web of Science, Trip, EBSCO, ClinicalTrials.gov and the Cochrane library was performed to identify research articles, only on human, published between January 1978 and August 2019. Search terms were pregnancy OR fertility OR fecundity OR fecundability, anti-Müllerian hormone OR AMH OR antral follicle count OR AFC OR ovarian reserve OR ovarian reserve test, in vitro fertilization OR ART OR assisted reproductive therapy OR assisted reproductive treatment OR assisted reproductive technology OR IVF OR ICSI, menstrual cycle length OR menstrual cycle characteristics. We combined these terms to complete the search. All prospective and retrospective studies exploring an association between MCL and proxies of ovarian reserve were included. The exclusions included studies of PCOS, ovarian failure, oral contraception treatment, prior chemotherapy and/or radiotherapy or ovarian surgery. The Newcastle–Ottawa scale was used to assess the quality of studies that were eligible for meta-analysis. OUTCOMES Eleven studies were eligible for meta-analysis, including 12 031 women. The included studies had a low risk of bias. Short MCL (21–27 days) was associated with lower ORT values as compared to normal (28–31 days), long (32–35 days) and all other (28–35 days) MCL sets. The estimated weighted mean difference (WMD) of AMH level was −1.3 ng/mL (95% CI: −1.75 to −0.86, P < 0.001) between the short and normal MCL sets. The estimated WMD of AFC values was −5.17 (95% CI: −5.96 to −4.37, P < 0.001) between the short and normal MCL sets. The weighted overall odds ratio (OR) of fecundability in natural cycles between women with short versus normal MCL sets was statistically significant (overall OR 0.81; 95% CI 0.72–0.91, P < 0.001). In the IVF setting, fewer oocytes were retrieved in short MCL in comparison to normal, long and all other MCL sets, with an estimated WMD of −1.8 oocytes (95% CI: −2.5 to −1.1, P < 0.001) in the short versus normal MCL sets. The weighted overall OR of clinical pregnancy rate between women with short versus all other MCL sets was statistically significant (overall OR 0.76; 95% CI: 0.60 to 0.96, P = 0.02). Low levels of heterogeneity were found in most meta-analyses of MCL and qualitative ovarian reserve biomarkers, while heterogeneity was high in meta-analyses performed for quantitative measures. WIDER IMPLICATIONS MCL in regularly cycling women is closely related to ovarian reserve biomarkers during the reproductive years. A short MCL, as compared to normal, is significantly associated with lower ORT values, reduced fecundability and inferior IVF outcomes, independent of age. The results imply that short MCL may be a sign of ovarian aging, combining the quantitative and qualitative facets of ovarian reserve. Educational efforts ought to be designed to guide women with short MCL at a young age, who desire children in the future, to seek professional counselling.


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


2021 ◽  
Vol 15 ◽  
pp. 263349412110241
Author(s):  
Mehtap Polat ◽  
Sezcan Mumusoglu ◽  
Irem Yarali Ozbek ◽  
Gurkan Bozdag ◽  
Hakan Yarali

Recent advances in our recognition of two to three follicular waves of development in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine and thereafter in women, luteal phase stimulation–derived oocytes are at least as competent as those retrieved following follicular phase stimulation. Poor ovarian responders still remain a challenge for many decades simply because they do not respond to ovarian stimulation. Performing follicular phase stimulation and luteal phase stimulation in the same menstrual cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes, which is a robust surrogate marker of live birth rate in in vitro fertilization across all female ages. Of interest, apart from one study, the bulk of evidence reports significantly higher number of oocytes following luteal phase stimulation when compared with follicular phase stimulation; hence, performing double stimulation/dual stimulation doubles the number of oocytes leading to a marked decrease in patient drop-out rate which is one of the major factors limiting cumulative live birth rates in such poor prognosis patients. The limited data with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness data are limitations of this novel approach. Double stimulation/dual stimulation is an effective strategy when the need to obtain oocytes is urgent, including patients with malignant diseases undergoing oocyte cryopreservation and patients of advanced maternal age or with reduced ovarian reserve.


1982 ◽  
Vol 99 (4) ◽  
pp. 481-486 ◽  
Author(s):  
S. Baumgarten ◽  
A. Römmler ◽  
K.G. Post ◽  
J. Hammerstein

Abstract. The objective of this study was to re-investigate the capacity of pituitary prolactin (Prl) and thyrotrophin (TSH) secretion throughout the normal menstrual cycle to respond to repeated thyrotrophin releasing hormone (TRH) stimulation analogous to the double luteinizing hormone-releasing hormone (LRH) stimulation test. This test has been shown to be a sensitive parameter for oestrogenic effects on the gonadotrophs. In addition, the volunteers were selected carefully on the basis of ovulatory cycles and otherwise normal endocrine function. In 9 women a combined LRH/TRH double stimulation test was performed during the early follicular, periovulatory and mid-luteal phases. TRH (200 μg) and LRH (25 μg) each were given iv twice, 2 h apart. Basal and LRH stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found to follow characteristic cyclic response patterns. The LH responses after both LRH stimulations were greatest in the periovulatory phase; Δ1 and Δ2 were higher in the mid-luteal phase than in the follicular phase. Maximum FSH response to LRH was found during the periovulatory phase, but the FSH response in the early follicular phase was greater than that found in the mid-luteal phase. In contrast, basal and TRH stimulated serum concentrations of TSH and Prl remained constant throughout the cycle. The gonadotrophin ratios Δ2:Δ1 were generally greater than 1. They increased from 1.4 in the early follicular phase to 3.0 in the late follicular phase, concomitant with the rise in oestrogens. The Δ2: Δ1 ratios for TSH and Prl were less than 1, ranging from 0.66 to 0.98 for TSH and from 0.26 to 0.99 for Prl. They did not show any cyclic changes. Thus, this study shows that after LRH/TRH double stimulation, the gonadotrophin but not the Prl and TSH responses vary with the physiological changes in oestrogens during the menstrual cycle. The supposed mechanism of oestrogen effects on pituitary hormone secretion and their possible clinical significance are discussed.


Author(s):  
A. Toledo ◽  
G. Stoelk ◽  
M. Yussman ◽  
R.P. Apkarian

Today it is estimated that one of every three women in the U.S. will have problems achieving pregnancy. 20-30% of these women will have some form of oviductal problems as the etiology of their infertility. Chronically damaged oviducts present problems with loss of both ciliary and microvillar epithelial cell surfaces. Estradiol is known to influence cyclic patterns in secretory cell microvilli and tubal ciliogenesis, The purpose of this study was to assess whether estrogen therapy could stimulate ciliogenesis in chronically damaged human fallopian tubes.Tissues from large hydrosalpinges were obtained from six women undergoing tuboplastic repair while in the early proliferative phase of fheir menstrual cycle. In each case the damaged tissue was rinsed in heparinized Ringers-lactate and quartered.


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