Luteal phase stimulation – an overview of the literature

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Luteal phase stimulation – an overview of the literature

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  • Research Article
  • Cite Count Icon 27
  • 10.1080/19396368.2018.1448902
Luteal-phase ovarian stimulation increases the number of mature oocytes in older women with severe diminished ovarian reserve
  • Mar 22, 2018
  • Systems Biology in Reproductive Medicine
  • Justin Rashtian + 1 more

ABSTRACTIn older women with severe diminished ovarian response (DOR), in vitro fertilization (IVF) treatment is much less successful due to the low number of mature oocytes collected. The objective of this study was to assess whether follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in the same menstrual cycle (double ovarian stimulation) in older women with severe DOR will produce a higher number of oocytes compared to FPS alone. Women with DOR (n = 69; mean age = 42.4) who underwent double ovarian stimulation for IVF were included. Women underwent ovarian stimulation in FPS using clomiphene citrate, letrozole, and gonadotropins followed by oocyte retrieval. The next day following oocyte retrieval, women underwent a second ovarian stimulation (LPS) using the same medications followed by a second oocyte retrieval. T-test was performed in order to compare the clinical characteristics and outcome in the same participant between FPS and LPS. Although antral follicle count at the start of FPS tended to be higher than at the start of the LPS cycle, there was no statistically significant difference between the duration of ovarian stimulation, peak estradiol levels, number of small (<14 mm) or large (≥ 14 mm) follicles, the total number of oocytes retrieved, or the total number of mature oocytes. Each woman had double the number of mature oocytes collected following a double ovarian stimulation compared to FPS alone. The addition of LPS to the conventional FPS increases the number of mature oocytes retrieved in the same IVF cycle, thus potentially increasing the chances of pregnancy in older women with severe DOR.Abbreviations: AFC: antral follicle count; BMI: body mass index; DOR: diminished ovarian reserve; E2: estradiol; FPS: follicular-phase stimulation; FSH: follicle stimulating hormone; GnRH: gonadotropin-releasing hormone; HCG: human chorionic gonadotropin; IRB: institutional review board; IVF: in vitro fertilization; LH: luteinizing hormone; LPS: luteal-phase stimulation; MII: metaphase II

  • Research Article
  • Cite Count Icon 45
  • 10.1093/humrep/deaa203
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.
  • Sep 20, 2020
  • Human Reproduction
  • Alberto Vaiarelli + 13 more

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.

  • Research Article
  • Cite Count Icon 207
  • 10.1016/j.fertnstert.2016.03.002
Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation
  • Mar 25, 2016
  • Fertility and Sterility
  • Filippo Maria Ubaldi + 9 more

Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation

  • Research Article
  • 10.1093/humrep/deae108.885
P-546 Do patients undergoing PGT-M benefit from the Duostim protocol?
  • Jul 3, 2024
  • Human Reproduction
  • L Kopcow + 10 more

Study question Do patients undergoing PGT-M benefit from the Duostim protocol? Summary answer PGT-M patients benefit because luteal phase stimulation is as effective as follicular phase stimulation in generating transferable embryos, thereby increasing the chances of treatment success. What is known already Patients undergoing PGT-M often require a larger number of embryos for pregnancy, with 25-50% deemed ineligible for transfer based on the disease indication (recessive, dominant, or sex-linked). DuoStim emerges as a valuable strategy for improving outcomes in poor responders. Progress in blastocyst culture, genetic testing, and vitrification motivates clinicians to optimize ovarian reserve exploitation through tailored stimulation protocols. Luteal Phase Stimulation (LPS) finds success in poor prognosis or oncological cases within DuoStim, a protocol widely used for poor prognosis patients necessitating both Follicular Phase Stimulation (FPS) and LPS. The potential benefits of DuoStim for PGT-M patients remain unexplored. Study design, size, duration Retrospective controlled case-control study conducted with paired FPS- and LPS-derived cohorts of oocytes collected in the same ovarian cycle (DuoStim). The study included 26 patients aged 36.53 ± 4,59 years old, undergoing DuoStim with the indication of PGT-M between July 2022 and October 2023. Participants/materials, setting, methods FPS and LPS were performed using the same daily dose of recombinant gonadotropins in an antagonist protocol. All zygotes underwent blastocyst culture, trophectoderm biopsy, vitrification, and subsequent thawing of one unaffected euploid blastocyst for transfer. The primary outcome was the mean number of transferable blastocysts (not affected euploid ones) obtained per oocyte retrieval from paired FPS- and LPS-derived cohorts. Secondary outcomes included the mean number of oocytes, blastocysts and implantation and pregnancy rates. Main results and the role of chance FPS and LPS were comparable regarding the mean number of mature oocytes collected (7.73 ± 4.27 vs. 7.57 ± 4.56) and the mean number of blastocysts obtained (3.27 ± 2.40 vs. 2.50 ± 1.98). The mean number of transferable blastocysts per retrieval were similar (FPS: 1.21 ± 1.31 vs. LPS: 0.78 ± 0.91). No significant differences in implantation or ongoing pregnancy rates were observed after transfers of euploid single blastocysts derived from FPS or LPS: 70.0% (7/10) vs. 57.14% (4/7). Three patients out of the 26 (11.54%) had transferable embryos only in the luteal phase. Limitations, reasons for caution Our findings warrant additional assessment through studies involving larger sample sizes. While our preliminary data indicate comparable implantation/pregnancy rates for PGT-M blastocysts from both FPS and LPS, further investigation is essential, especially in populations beyond those with a reduced number of usable blastocysts Wider implications of the findings These data underscore that oocytes obtained from LPS are as competent as those derived from FPS. Patients with unaffected euploid embryos solely due to FLS would not have had any transfer without DuoStim. This protocol could be advantageous for women abroad or with time constraints, potentially reducing dropout rates. Trial registration number Not applicable

  • Research Article
  • Cite Count Icon 1
  • 10.1080/09513590.2021.1922885
Dydrogesterone primed luteal phase stimulation may be better than follicular phase stimulation in patients with diminished ovarian reserve
  • May 4, 2021
  • Gynecological Endocrinology
  • Hulusi Bulent Zeyneloglu + 4 more

Objective In this study, we aimed to compare the efficacy of luteal phase stimulation (LPS) and follicular phase stimulation (FPS) in two separate menstrual cycles (2–5 months intervals) of the same patient, utilizing LPS with dydrogesteron only. Methods This retrospective case control study was conducted with patients with diminished ovarian reserve (DOR) (Group 1) and infertile patients with Anti-Müllerian hormone >1.2 ng/mL (Group 2) undergoing two ovarian stimulations (FPS and LPS with dydrogesteron only) and two oocyte retrievals in two separate menstrual cycles (2–5 months intervals) in the Division of Reproductive Endocrinology and Infertility of Baskent University, Ankara, between April 2019 and December 2019. Results In group 1, the number of frozen embryos was significantly higher in LPS when compared to FPS; 1.71 vs. 0.54, (p < .001), respectively. In group 2, the number of frozen embryos was higher in LPS when compared to FPS (0.8 vs. 0.4) however the difference did not reach a statistical significance (p: 0.157). Conclusion LPS may be beneficial especially in the patients with diminished ovarian reserve with follicular asynchronization in the menstrual onset. In addition, it should be kept in mind that dydrogesterone only may be used instead of gonadotropin-releasing hormone antagonist to prevent possible luteinizing hormone rise in LPS.

  • Research Article
  • 10.1093/humrep/deab130.606
P–607 luteal phase stimulation results in similar euploid blastocysts rate vs. conventional stimulation: donor-recipient cycles
  • Aug 6, 2021
  • Human Reproduction
  • B Martazanova + 4 more

Study question Does the luteal phase stimulation (LPS) impact the embryological outcomes, euploid blastocyst rate, and pregnancy rate compared to conventional stimulation in donor-recipient cycles? Summary answer LPS is associated with similar embryological outcomes, euploid blastocyst rate, and pregnancy rate among the corresponding recipients compared to stimulation in the follicular phase. What is known already LPS has been suggested for fertility preservation in cancer patients, but now it is a part of the new double-stimulation strategy applied to poor responders. Some studies found no difference in the number of oocytes retrieved with LPS compared to conventional stimulation. According to other data, LPS increased numbers of retrieved oocytes compared to follicular stimulation (FPS). Previous studies showed a similar euploid blastocyst formation rate after LPS using the DuoStim approach in poor prognosis patients. However, there is limited data about the embryological outcomes and IVF treatment success in patients with normal ovarian reserve undergoing the LPS. Study design, size, duration This prospective observational study included 25 oocyte donors. Group 1 (n = 12) received stimulation on day 2 follicular phase. In group 2 (n = 13) received the stimulation on 2–4 day after the ovulation. The definition of spontaneous ovulation included the presence of collapsed follicle/corpus luteum in an ultrasound examination, an increase in the serum P level ≥ 2.0 ng/mL. The blastocyst biopsy and aneuploidy screening were performed for 63 embryos. Participants/materials, setting, methods Inclusion criteria: age 18–35 years; basal FSH&amp;lt;10 IU/ml; regular cycle; spontaneous ovulation; AFC&amp;gt;10; normal karyotype; physically and mentally healthy. Exclusion criteria: uterine fibroids; deep endometriosis; PCOS; reduce ovarian reserve. Blastocysts were graded using the Gardner and Schoolcraft classification. Trophectoderm biopsy was performed using the Octax lazer (Sweden). Detection of aneuploidies was performed using the ReproSeq PGS Kit according to the manufactures instruction. Aneuploidy haplotyping was done using Applied Biosystems (4-capillary) Genetic Analyzer. Main results and the role of chance No statistically significant differences were found in the number of mature oocytes (20.1±5.58 vs. 21.00±6.1,p=1.0), in the number of donated oocytes (6.17±2.3 vs. 5.7±2.01,p=0.57), in an average number of the blastocyst (4.58 ± 2.2 vs. 3.84 ± 1.8, P = 0.43), in an average number of the euploid blastocyst (1.9 ±1.3 vs. 1.7 ± 1.2, P = 0.78) from FPS versus LPS stimulation, respectively. The euploid blastocyst rate calculated per donated oocytes (30.4% vs. 31.8%,p=1.0), the euploid blastocyst rate calculated per two-pronuclear zygote (31.8% vs. 38%,p=0.56), the euploid blastocyst rate calculated per biopsied blastocyst (63.6% vs. 70%, p = 0.78) also were similar after FPS and LPS stimulation. There were no differences between the groups of recipients in fertilization rate (95.7% vs. 83%, p = 0.13). Only one embryo was transferred in artificial frozen-thawed embryo transfer to corresponding recipients. The pregnancy rate per embryo transfer was comparable in both groups ((64% (7/11), 95%CI: 30.8–89.0 vs. 62.5% (5/8), 95%CI: 24.5–91.5, p = 1.0, in group I and II, respectively). Limitations, reasons for caution Our study was carried out in a relatively small subset of patients; therefore, obtained results cannot be extrapolated on other groups of patients and need to be confirmed in larger trials. Wider implications of the findings: This study opens new possibilities for investigating the luteal. phase stimulation impact on oocyte competence and embryo development Trial registration number approved by the ethics committee and Institutional Review Board at 07.09.2017 protocol №10 of Kulakov National Medical Research Centre of Obstetrics, Gynecology and Perinatology. All participants provided written consent.

  • Research Article
  • 10.1093/humrep/deaf097.747
P-441 Clinical results from a double ovarian stimulation protocol involving follicular and a subsequent luteal phase stimulation in poor reproductive prognosis patients
  • Jun 1, 2025
  • Human Reproduction
  • K Litwicka + 5 more

Study question Which patients having poor reproductive prognosis might benefit from a follicular phase stimulation (FPS) and subsequent luteal phase stimulation (LPS) performed in the same cycle? Summary answer The female age, more than AMH, predicts the prognosis for obtaining euploid blastocysts, in a duostim protocol. What is known already The standard DuoStim protocol involves the FPS and LPS performed in the same ovarian cycle. LPS contributes to conventional stimulation by producing more oocytes of comparable competence in terms of blastulation and euploidy rate. Double ovarian stimulation allows to achieve a pregnancy in a short period of time and is considered a valuable option for poor prognosis patients. However, no study has evaluated the patients' baseline data or the first ovarian stimulation characteristics to identify patients who could truly benefit from a second stimulation in the same cycle. Study design, size, duration A retrospective proof-of-concept matched case-control study was conducted at a single IVF center between May 2020 and September 2023. All poor prognosis patients were counseled regarding the high risk of embryo aneuploidy and were informed about the possibility of starting a second stimulation immediately to optimize PGT-A results. One hundred seventy patients underwent two consecutive ICSI/PGT-A treatments. Participants/materials, setting, methods The FPS initiated on day two of the menstrual cycle and LPS started four/five days after the first oocyte retrieval. Both stimulations were performed in a flexible antagonist protocol. All embryos were cultured until the blastocyst stage for a trophectoderm biopsy for PGT-A and cryopreserved by a vitrification method. The biopsy samples of all blastocysts were analyzed together. The frozen-thawed transfers of euploid blastocysts were performed in GnRH-agonist/estradiol valerate prepared protocol. Main results and the role of chance Patients’ mean age and AMH were 39.9±3.5 years and 1.1±0.8 ng/ml, respectively. The number of all oocytes, MII oocytes, and their fertilization rate were significantly higher in LPS (6.3±3.8 vs 4.3±2.9, 5.1±3.2 vs 3.1±2.3, and 66.0% vs 64.5%, respectively). The mean number of frozen blastocysts and the rate of euploid blastocysts were comparable in both stimulations. The overall and clinical pregnancy rates from transfers of euploid blastocysts obtained from FPS and LPS were similar (70% vs 80% and 60% vs 70%, respectively). Thirty-five percent of women did not obtain blastocysts from FPS. Their mean age was significantly higher compared to the patients who had embryos for analysis (41.4±2.7 vs 38.9±3.6 years). In LPS, 61.3% of them formed blastocysts, and 21.0% had healthy embryos, with a subsequent clinical pregnancy rate of 75%. Forty-eight percent of women did not obtain euploid blastocysts from FPS. All these patients were older than 42 years. In LPS, 23.3% of them formed euploid embryos, with a subsequent clinical pregnancy rate of 70%. The AMH value was similar in patients who obtained embryos and those who did not, as well as in those who had healthy and unhealthy embryos. Limitations, reasons for caution These results should be evaluated with caution as the study is retrospective and performed in a small population. Further prospective randomized studies in a higher sample size are needed to verify if double ovarian stimulation might represent a protocol for older patients with poor results from FPS Wider implications of the findings This study documents that female age, more than AMH, predicts the prognosis for obtaining healthy embryos. Double ovarian stimulation is a valuable option to improve the chances of euploid blastocyst transfer in older women. This protocol improves treatment success in poor prognosis patients willing to conceive with own oocytes Trial registration number No

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  • Research Article
  • Cite Count Icon 18
  • 10.1186/s12958-020-00655-3
The best execution of the DuoStim strategy (double stimulation in the follicular and luteal phase of the same ovarian cycle) in patients who are poor ovarian responders
  • Oct 15, 2020
  • Reproductive Biology and Endocrinology
  • Yanqun Luo + 7 more

BackgroundPatients found to be poor ovarian responders (POR) are a challenging patient population for any assisted reproduction technology. Despite attempts at various controlled ovarian stimulation schemes, reproductive outcomes in this patient population have not improved. In recent years, the DuoStim protocol (both follicular and luteal phase stimulation during the same menstrual cycle) has shown a potential for use in patients with POR.MethodsThis retrospective study reviewed the medical records of 304 women who were diagnosed as POR and underwent the DuoStim protocol. We compared follicular phase stimulation (FPS) data and luteal phase stimulation (LPS) data of the same patients. We also compared the effects of different trigger drugs including urine human chorionic gonadotropin (uHCG; 10,000 IU), recombinant human chorionic gonadotropin (rHCG; 250 μg), and gonadotropin-releasing hormone agonist (GnRH-a; 0.2 mg) at the FPS and LPS stages.ResultsPOR undergoing the DuoStim protocol resulted in a significantly higher number of oocytes retrieved, normal fertilised oocytes, cleaved embryos, cryopreserved embryos, and good quality embryos at the LPS stage than at the FPS stage. Trigger drugs at the FPS stage did not affect the FPS stage data. Regardless of the stage, rHCG and GnRH-a yielded significantly more cryopreserved embryos and good quality embryos than uHCG.ConclusionThe use of GnRH-a or rHCG as the trigger drug may be better than uHCG in both the FPS and LPS stages for POR undergoing the DuoStim protocol. This will increase the number of good quality embryos at the LPS stage. We found that the LPS stage results in more oocytes (and therefore more embryos) than the FPS stage.

  • Research Article
  • Cite Count Icon 24
  • 10.1016/j.rbmo.2012.11.020
Flexible ovarian stimulation in a poor responder: a case report and literature review
  • Dec 8, 2012
  • Reproductive BioMedicine Online
  • Bin Xu + 1 more

Flexible ovarian stimulation in a poor responder: a case report and literature review

  • Research Article
  • Cite Count Icon 3
  • 10.1093/humrep/deae165
Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.
  • Jul 17, 2024
  • Human reproduction (Oxford, England)
  • B Lawrenz + 6 more

What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. The retrospective study design and the small sample size can limit the accuracy of the estimates. Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. This study did not receive funding. The authors declare that there is no conflict of interest. N/A.

  • Research Article
  • Cite Count Icon 2
  • 10.4103/jhrs.jhrs_76_23
Luteal Phase Stimulation in the Same Cycle Is an Effective Strategy to Rescue POSEIDON Poor Responders with No Embryos after the First Follicular Stimulation
  • Jan 1, 2023
  • Journal of Human Reproductive Sciences
  • Abha Majumdar + 5 more

Background:Poor responders may benefit from recruiting a ‘second wave’ of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been named as ‘DuoStim’. This protocol involves ovarian stimulation in both follicular and luteal phases with egg retrieval in each phase, respectively, to increase the number of oocytes and embryos in one menstrual cycle. This can be considered a potentially valuable option for women with poor ovarian reserve/response to maximise the number of oocytes retrieved in a single ovarian cycle in the shortest possible time.Aims:The aim of this study was to evaluate the efficacy of the DuoStim protocol in women classified as POSEIDON poor responders undergoing in vitro fertilization by comparing the embryological outcomes between the follicular and luteal phase stimulations in the same menstrual cycle.Settings and Design:This was a retrospective cohort study of 131 patients who enrolled to undergo DuoStim cycles from January 2021 to Sept. 2022, at a IVF center in a tertiary care hospital.Materials and Methods:The follicular phase stimulation used a standard antagonist protocol for the first oocyte retrieval. Thereafter, the luteal phase stimulation was started 3 days after the first retrieval, with the same dose of gonadotropin along with a daily 10 mg medroxyprogesterone acetate tablet, followed by a second oocyte retrieval. Blastocysts produced in both the phases were subsequently vitrified.Statistical Analysis Used:The paired t-test was used for comparing means and 95% confidence intervals (CIs) for different parameters. McNemar's test was used to compare paired proportions. The analysis was conducted using R statistical environment 4.2.Results:The mean number of oocytes retrieved and the mean number of utilizable blastocysts frozen per stimulation cycle were found to be significantly higher in the luteal phase as compared to the follicular phase (5.71 ± 3.95 vs. 4.87 ± 2.79, P = 0.02, and 1.43 ± 1.22 vs. 0.95 ± 1, P = 0.001, respectively). However, the mean fertilization rate and the mean blastocyst utilization rate were found to be similar between both the phases. The length of stimulation was found to be approximately 3 days longer in the luteal phase (12.63 ± 2.43 vs. 9.75 ± 1.85, P = 0.001). Overall, the odds of obtaining a usable blastocyst in the luteal phase was found to be significantly higher than in the paired follicular phase (73.9% vs. 57.7%, P = 0.012, odds ratio: 2.286 [95% CI: 1.186–4.636]). Also importantly, the luteal phase stimulation was able to rescue 68% (32/47) of patients where no blastocysts were formed in the follicular phase.Conclusion:Our data demonstrate that in women with poor reserve, the addition of luteal stimulation could increase the chances of achieving a pregnancy by significantly increasing the number of eggs and transferable embryos per menstrual cycle compared to follicular stimulation alone. Furthermore, luteal phase stimulation in the same cycle proved to be an effective strategy to rescue POSEIDON poor responders with no embryos after the first stimulation.

  • Research Article
  • Cite Count Icon 5
  • 10.1016/j.jogoh.2018.11.003
Luteal phase stimulation, the future of fertility preservation? Retrospective cohort study of luteal phase versus follicular phase stimulation
  • Nov 12, 2018
  • Journal of Gynecology Obstetrics and Human Reproduction
  • Floriane Jochum + 5 more

Luteal phase stimulation, the future of fertility preservation? Retrospective cohort study of luteal phase versus follicular phase stimulation

  • Abstract
  • 10.1016/j.fertnstert.2021.07.988
LUTEAL PHASE STIMULATION PROVIDES HIGHER MATURE OOCYTE AND BLASTOCYST YIELD IN PATIENTS UNDERGOING A DOUBLE STIMULATION IN THE SAME OVARIAN CYCLE (DUOSTIM) PROTOCOL
  • Sep 1, 2021
  • Fertility and Sterility
  • Jose Antonio Moreno-Sepulveda + 6 more

LUTEAL PHASE STIMULATION PROVIDES HIGHER MATURE OOCYTE AND BLASTOCYST YIELD IN PATIENTS UNDERGOING A DOUBLE STIMULATION IN THE SAME OVARIAN CYCLE (DUOSTIM) PROTOCOL

  • Research Article
  • Cite Count Icon 1
  • 10.1093/humrep/deac104.085
O-071 In progestin primed double stimulation protocol: Is luteal phase stimulation more effective than follicular phase stimulation in poor responders? A randomized controlled study
  • Jun 29, 2022
  • Human Reproduction
  • A Hussein + 3 more

Study question Is follicular phase or luteal phase stimulation more effective in progestin primed double stimulation protocol in poor responders? Summary answer The luteal phase stimulation was more effective than follicular phase stimulation in the progestin primed dual stimulation protocol in poor responders. What is known already Poor ovarian responders involve 9–24% of patients undergoing in vitro fertilization (IVF), with the management of these patients posing an everyday practical challenge. Owing to the follicular waves theory, two or three waves of folliculogenesis were detected during the interovulatory interval, two consecutive ovarian stimulation protocols could be initiated in the follicular phase and the subsequent luteal phase. This is an effective way to increase the number of oocytes and embryos obtained over a relative short period of time. Furthermore, there is increasing evidence that progestins can be a reliable method of preventing premature LH surge during ovarian stimulation. Study design, size, duration This was a randomized controlled study performed at the Infertility and Assisted Reproduction Unit of ElShatby Maternity Hospital, Alexandria University and Madinah Fertility Centre. The study was conducted on 90 infertile women with poor ovarian response as defined by the Bologna criteria. 7 patients were excluded due to protocol violation, loss to follow-up and patient withdrawal. The study commenced in September 2020 and was finalized in September 2021. Participants/materials, setting, methods Group 1 45 patients were given the progestin primed double stimulation protocol. Dydrogesterone was started from the first day of the ovulation induction till the end of luteal phase stimulation. Embryo transfer was scheduled in a subsequent cycle. Group 2 45 patients were given the flexible GnRh antagonist protocol in 2 cycles. The best blastocyst from either cycle was transferred in the second cycle. Main results and the role of chance When comparing the follicular and luteal phases, the M2 oocytes number retrieved in the luteal phase was statistically significantly higher than the follicular phase, with the median number of 4 oocytes against a median number of 2 oocytes (P value 0.001). The fertilization rate was significantly higher in the M2 oocytes of the luteal phase stimulation (P value 0.04). The resultant embryos from the luteal stimulation phase were statistically significantly higher than the follicular phase, with the median number of 3 embryos against a median number of 1 embryo (P value &amp;lt;0.001). However, we found that the days of controlled ovarian hyperstimulation were statistically significant higher in stimulation of the luteal phase with the median of 12 days against the 10 days seen in follicular phase stimulation (P value 0.002). Consequently, the total dosage of gonadotropins was statistically significant higher in the luteal phase with a P value of 0.007. After Subgroup analysis, Poseidon Group 4 patients demonstrated that a significantly higher number of oocytes were retrieved after the progestin primed double stimulation than after two waves of flexible GnRh antagonist stimulation (median of 12 oocytes against a median of 10 oocytes with P value 0.01). Limitations, reasons for caution Firstly, preimplantation genetic testing was not performed to detect euploid embryos which could be vital when comparing both the phases and the protocols. Secondly, despite the importance of the live birth rate as an outcome measure, we did not enroll this measure. Wider implications of the findings In the light of our findings, we recommend the usage of progestin primed dual stimulation protocol in poor responder patients. Additionally, we call for multicentric randomized controlled research to verify this protocol as a first-line treatment protocol in poor responder patients. Trial registration number ClinicalTrials.gov ID: NCT04537078

  • Research Article
  • Cite Count Icon 12
  • 10.1080/09513590.2020.1822804
DuoStim cycles potentially boost reproductive outcomes in poor prognosis patients
  • Sep 21, 2020
  • Gynecological Endocrinology
  • Gustavo N Cecchino + 6 more

Aim To evaluate the overall performance and oocyte quality of follicular phase stimulation (FPS) vs. luteal phase stimulation (LPS) among patients undergoing double ovarian stimulation (DuoStim). Materials and methods Observational retrospective two-center cohort study including 79 infertile women who underwent a total of 87 DuoStim cycles between January 2017 and May 2019. Besides assessing baseline characteristics in order to determine the patients’ clinical profile, we analyzed the FPS and LPS regarding the total dose of gonadotropin received, the duration of stimulation, the number and maturity of oocytes, fertilization and blastocyst formation rates, and the number of blastocysts obtained. Results The patients’ baseline characteristics were compatible with a diminished ovarian reserve and poor reproductive prognosis. While the luteal phase needed longer stimulation (12 days (5–19) vs. 11 (7–16), p < .001) and slightly higher gonadotropin doses (2946 ± 890 IU vs. 2550 ± 970 IU, p < .001), no significant differences were detected in the oocyte maturity, fertilization, and blastocyst formation rates. However, the number of oocytes retrieved (5 (0–16) vs. 4 (0–15), p = .006), mature oocytes (4 (0–15) vs. 3 (0–11), p = .032), and blastocysts obtained (70 vs. 53) were substantially greater after LPS. Conclusions The DuoStim strategy in poor prognosis patients increases the number of oocytes and blastocysts available. Moreover, the number of oocytes and blastocysts obtained are higher after LPS when compared to FPS. Thus, it should be considered for selected patients in order to not only improve reproductive outcomes but also shorten the time to pregnancy.

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