InfertilityPhase 4DUO_STIM_FRESHNCT04446845
Double Stimulation Followed by a Fresh Embryo Transfer
A Phase 4 study testing Double Stimulation (Elonva+rFSH) in luteal /follicular phase and Conventional Stimulation (Elonva+rFSH) in follicular phase in people with Infertility, run by Fundación Santiago Dexeus Font at 1 site in Spain.
Trial summary
The major goal of controlled ovarian stimulation (COS) is to increase the number of oocytes harvested in order to result in the generation of a higher number of available embryos, extended embryo culture, embryo selection and finally providing higher cumulative live birth rates in infertile patients. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Double Stimulation (Elonva+rFSH) in luteal /follicular phase and Conventional Stimulation (Elonva+rFSH) in follicular phase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- 30 Oct 2020to 2 May 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Poor prognosis patients according to the POSEIDON group 3 \& 4 (based on AMH)
- AMH <1.2
- age <40 years old
- BMI >18 and <35 kg/m2
- Body weight >50kg (in women <36 years old body weight >60kg)
Who cannot join
- Maternal age > 40 years
- History of untreated autoimmune, endocrine or metabolic disorders
- Previous ovarian cystectomy or oophorectomy
- Body weight <50kg (and body weight <60kg in women <36 years old)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double vs. Single Stimulation in Young Poor Prognosis Patients Followed by a Fresh Embryo Transfer. A Randomized Clinical Trial
The major goal of controlled ovarian stimulation (COS) is to increase the number of oocytes harvested in order to result in the generation of a higher number of available embryos, extended embryo culture, embryo selection and finally providing higher cumulative live birth rates in infertile patients. Moreover, with the idea of the multiple waves of follicular production, we could start to take full advantage of the whole follicular cohort, and not only of the follicular wave.
In the context of low prognosis women such as women with poor ovarian response where, the success rates are very low due to the low number of oocytes retrieved and consequently of viable embryos), Dual stimulation may be of great value as a tool to improve outcomes.
The reported advantage of DuoStim is retrieved of more oocytes within a shorter time span, resulting in an increase in the probability of having transferable embryos increases, and theoretically reducing time to live birth as well as cycle cancellation.
Read the detailed description
In assisted reproductive technologies (ART), despite the progress of the last decades, the achievement of a live birth still remains a challenge, especially for some categories of patients such as the one with poor ovarian reserve. One of the main tolls in reproductive medicine is controlled ovarian stimulation (COS) which is performed with the aim of obtaining multiple oocytes, so as to increase the chance of a live birth (LB) .
In order to induce multifollicular development in ovarian stimulation, recombinant FSH (or other products based on FSH) are given at the beginning of the follicular phase for an average of 10-12 days. The reason for this timing is mainly due to the fact that the follicular phase is clearly the moment when the ovaries are recruiting new follicles in order to establish the dominant for the cycle. However, as previously described follicular production by the ovaries follows a pattern of multicyclic waves. More specifically, a wave is a synchronous growth of follicles that have similar diameter and that can be documented with ultrasound . Beside the very well-known follicular wave (which is the one exploited in the COS), 64% of the women has two waves (follicular and luteal) and 32% of women has up to 3 waves in a normal cycle (early follicular, late follicular and luteal) .
The innovative concept of multiple waves of follicular development has been utilized in previous studies aiming to evaluate the effect of more than 1 stimulation cycles in a short period of time (less than 1 month). Specifically, two stimulation cycles have been performed in the same cycle by previous researcher (starting from the classical follicular COS and followed by a subsequent stimulation 5 days after the first oocyte retrieval) and it has been shown to be associated with improved cycle outcomes, alias higher number of oocytes retrieved and number of embryos obtained in total. Furthermore, in women with low ovarian response recent studies have suggested that the luteal phase stimulation appears to result in a higher number of oocytes retrieved as compared to the first follicular phase stimulation cycle .
Nevertheless, in spite of the accumulating evidence, a common characteristic of all of the published trials up to date is that in all of them dual stimulation cycle was initiated in the classical follicular phase followed by second stimulation cycle 5 days after oocytes retrieval. This approach had two major limitations:
- Owing to this extended protocol and the luteal phase start the lack of synchronization between embryos and endometrium, a freeze-only protocol was considered essential to be adopted .
- The fact that the 2nd stimulation cycle (luteal phase) always started 5 days after the first stimulation cycle does allow an unbiased evaluation of whether the improved outcomes on the second cycle are attributed to the luteal phase initiation of stimulation or to a carry-over effect of the first stimulation cycle.
Based on the above evidence we decided to design the current randomized trial which is, to our knowledge, the first to evaluate the benefit from the dual stimulation approach, not followed by a freeze-only strategy, but by fresh embryo transfer. In order to achieve this, we aim to compare the COS with the double stimulation (first luteal stimulation and then follicular ovarian stimulation) followed by fresh embryo transfer (ET) in poor prognosis patients undergoing in vitro fertilization/intra-cytoplasmatic sperm injections (IVF/ICSI) treatment.
The current randomized trial will allow us to
- compare the double stimulation with a single stimulation strategy followed by fresh embryo transfer and
- perform comparison of a luteal phase (1st cycle of the double stimulation group) and a follicular phase stimulation (control group) in a randomized setting
- Conditions
- Infertility
- Being tested
- Double Stimulation (Elonva+rFSH) in luteal /follicular phase, Conventional Stimulation (Elonva+rFSH) in follicular phase
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double Stimulation (Elonva+rFSH) in luteal /follicular phaseDrug
Following the 2nd oocyte retrieval, the patient will start luteal phase support (LPS) with vaginal micronized progesterone 200mg x 3 times a day until the day of the pregnancy test. All embryos will be cultured until day 5 in time-lapse incubators. In case of no blastocyst in the second cycle, or in case of poor embryo quality and in case of availability of frozen embryos from the first stimulation cycle, 1 frozen blastocyst from the first cycle will be thawed and will be transferred 5 days following the 2nd oocyte retrieval. Embryo transfer will be performed in all patients with available blastocysts, except in cases of high risk of ovarian hyperstimulation syndrome (OHSS) or progesterone elevation which is considered clinically relevant on the day of human chorionic gonadotropin (hCG) trigger, in which freeze-all strategy and deferred frozen embryo transferred will be considered.
Conventional Stimulation (Elonva+rFSH) in follicular phaseDrug
From the day of oocyte retrieval, the patients will be asked to start the LPS with vaginal micronized progesterone 3 times a day until the day of the pregnancy test. Embryo transfer will be performed in all patients with available blastocysts, except in cases of high risk of OHSS or progesterone elevation which is considered clinically relevant on the day of hCG trigger, in which freeze-all strategy and deferred frozen embryo transferred will be considered.
| Study group | Role | What they receive |
|---|---|---|
| Double Stimulation (Elonva+rFSH) in luteal /follicular phase | Experimental | A first stimulation Stimulation will initiate in the luteal phase of the menstrual cycle On day 21 of the previous cycle150mcg of corifollitropin alfa (Elonva, Merck Sharp \& Dohme (MSD), Spain) will be administrated and from day 8 of the stimulation when necessary, r-FSH of 250 IU per day will start until the day of ovulation trigger in a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol. The first ovulation triggering will be induced with GnRH-agonist (triptorelin 0.2 ml). The embryos obtained from the first stimulation will be cryopreserved in a freeze-all approach.
A second stimulation will start on day 2 of bleeding after the first oocyte retrieval.
This time will correspond to a conventional COS where corifollitropin alfa will be administered on the beginning of the follicular phase, in a flexible antagonist protocol, and the second ovulation will be triggered with 250μg of Recombinant Human Chorionic Gonadotropin (rhCG) Receives: Drug: Double Stimulation (Elonva+rFSH) in luteal /follicular phase |
| Conventional Stimulation (Elonva+rFSH) in follicular phase | Active comparator | A conventional COS where Corifollitropin alfa will be administered on the beginning of the follicular phase, in a flexible antagonist protocol, and the second ovulation will be triggered with 250μg of rhCG Receives: Drug: Conventional Stimulation (Elonva+rFSH) in follicular phase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of good-quality blastocysts
Embryo quality will be assessed according to the Istanbul consensus workshop criteria (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Human Reproduction 2011) and good quality embryo (GQE) at this developmental will be an expanded through to hatched blastocyst with an inner cell mass (ICM) that is prominent, easily discernible and consisting of many cells, with the cells compacted and tightly adhered together, and with a trophectoderm (TE) that comprises many cells forming a cohesive epithelium
Measured: Day of embryo transfer (9 -20 days from initiation of the last ovarian stimulation)
Secondary outcomes (10)
Number oocytes retrieved
The outcome will be evaluated on the day of oocyte retrieval
Measured: 9 -20 days from initiation of the last ovarian stimulation
Number of cycles reaching the stage of embryo transfer
The outcome will be evaluated 5 days after last oocyte retrieval
Measured: 9 -20 days from initiation of the last ovarian stimulation
Clinical pregnancy
The presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 6-7 weeks of gestation
Measured: 6-7 weeks of gestation
Ongoing pregnancy
The presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 11-12 weeks of gestation
Measured: 8-10 weeks of gestation
Time to pregnancy
Days between beginning of first stimulation and clinical pregnancy
Measured: 4-6 weeks of gestation
Number of oocytes between follicular phase or luteal phase initiation of ovarian stimulation
The outcome will be evaluated on the day of oocyte retrieval
Measured: 9 -20 days from initiation of the ovarian stimulation
Number of Metaphase II oocytes (MII) between follicular phase or luteal phase initiation of ovarian stimulation
The outcome will be evaluated on the day of oocyte retrieval
Measured: 9 -20 days from initiation of the ovarian stimulation
Total additional dose of recombinant follicle stimulating hormone (rFSH)
The outcome will be evaluated on the day of trigger
Measured: 9 -20 days from initiation of the ovarian stimulation
Length of stimulation
The outcome will be evaluated on the day of trigger
Measured: 9 -20 days from initiation of the ovarian stimulation
Endocrine profile
Estradiol, Progesterone, luteinizing hormone (LH) and FSH
Measured: Day 1, Day 6 , Day 8 of stimulation and Day of trigger 9 -20 days from initiation of the ovarian stimulation in each ovarian stimulation cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start30 Oct 2020
- Primary completion15 Jan 2023
- Study completion2 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Santiago Dexeus Font
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Nikolaos P Polyzos, MD PhD, Study director, Hopital Universitari Dexeus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04446845
- Sponsor's protocol ID
- FSD-DUO-2020-02
- Acronym
- DUO_STIM_FRESH
- Status last verified
- May 2023
- First submitted
- 19 Jun 2020
- Last updated
- 15 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alsbjerg B, Haahr T, Elbaek HO, Laursen R, Povlsen BB, Humaidan P. Dual stimulation using corifollitropin alfa in 54 Bologna criteria poor ovarian responders - a case series. Reprod Biomed Online. 2019 May;38(5):677-682. doi: 10.1016/j.rbmo.2019.01.007. Epub 2019 Jan 22.
PubMed 30795977Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.
PubMed 21502182Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
PubMed 12849812Cardoso MCA, Evangelista A, Sartorio C, Vaz G, Werneck CLV, Guimaraes FM, Sa PG, Erthal MC. Can ovarian double-stimulation in the same menstrual cycle improve IVF outcomes? JBRA Assist Reprod. 2017 Sep 1;21(3):217-221. doi: 10.5935/1518-0557.20170042.
PubMed 28837031Coutifaris C. Freeze-only in vitro fertilization cycles for all? Fertil Steril. 2017 Aug;108(2):233-234. doi: 10.1016/j.fertnstert.2017.06.028. No abstract available.
PubMed 28778278Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, Polyzos NP. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016 Feb;31(2):370-6. doi: 10.1093/humrep/dev316. Epub 2016 Jan 2.
PubMed 26724797Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
PubMed 21505041Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.
PubMed 24161646Liu C, Jiang H, Zhang W, Yin H. Double ovarian stimulation during the follicular and luteal phase in women >/=38 years: a retrospective case-control study. Reprod Biomed Online. 2017 Dec;35(6):678-684. doi: 10.1016/j.rbmo.2017.08.019. Epub 2017 Aug 24.
PubMed 29030068Moffat R, Pirtea P, Gayet V, Wolf JP, Chapron C, de Ziegler D. Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited. Reprod Biomed Online. 2014 Dec;29(6):659-61. doi: 10.1016/j.rbmo.2014.08.010. Epub 2014 Sep 4.
PubMed 25311972Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT, Seli E. Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance. Hum Reprod. 2018 Aug 1;33(8):1489-1498. doi: 10.1093/humrep/dey238.
PubMed 30010882Polyzos NP, Nwoye M, Corona R, Blockeel C, Stoop D, Haentjens P, Camus M, Tournaye H. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014 Apr;28(4):469-74. doi: 10.1016/j.rbmo.2013.11.010. Epub 2013 Dec 4.
PubMed 24581984Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number); Alviggi C, Andersen CY, Buehler K, Conforti A, De Placido G, Esteves SC, Fischer R, Galliano D, Polyzos NP, Sunkara SK, Ubaldi FM, Humaidan P. A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept. Fertil Steril. 2016 Jun;105(6):1452-3. doi: 10.1016/j.fertnstert.2016.02.005. Epub 2016 Feb 26. No abstract available.
PubMed 26921622Sighinolfi G, Sunkara SK, La Marca A. New strategies of ovarian stimulation based on the concept of ovarian follicular waves: From conventional to random and double stimulation. Reprod Biomed Online. 2018 Oct;37(4):489-497. doi: 10.1016/j.rbmo.2018.07.006. Epub 2018 Aug 11.
PubMed 30170909Tsampras N, Gould D, Fitzgerald CT. Double ovarian stimulation (DuoStim) protocol for fertility preservation in female oncology patients. Hum Fertil (Camb). 2017 Dec;20(4):248-253. doi: 10.1080/14647273.2017.1287433. Epub 2017 Feb 9.
PubMed 28423955
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double vs. Single Stimulation in Young Poor Prognosis Patients Followed by a Fresh Embryo Transfer. A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04446845
- Acronym / sponsor ID
- DUO_STIM_FRESH / FSD-DUO-2020-02
- Conditions
- Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Fundación Santiago Dexeus FontUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 30 Oct 2020 (actual)
- Primary completion
- 15 Jan 2023 (actual)
- Study completion
- 2 May 2023 (actual)
- First posted
- 25 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The major goal of controlled ovarian stimulation (COS) is to increase the number of oocytes harvested in order to result in the generation of a higher number of available embryos, extended embryo culture, embryo selection and finally providing higher cumulative live birth rates in infertile patients. Moreover, with the idea of the multiple waves of follicular production, we could start to take full advantage of the whole follicular cohort, and not only of the follicular wave.
In the context of low prognosis women such as women with poor ovarian response where, the success rates are very low due to the low number of oocytes retrieved and consequently of viable embryos), Dual stimulation may be of great value as a tool to improve outcomes.
The reported advantage of DuoStim is retrieved of more oocytes within a shorter time span, resulting in an increase in the probability of having transferable embryos increases, and theoretically reducing time to live birth as well as cycle cancellation.
Detailed description
In assisted reproductive technologies (ART), despite the progress of the last decades, the achievement of a live birth still remains a challenge, especially for some categories of patients such as the one with poor ovarian reserve. One of the main tolls in reproductive medicine is controlled ovarian stimulation (COS) which is performed with the aim of obtaining multiple oocytes, so as to increase the chance of a live birth (LB) .
In order to induce multifollicular development in ovarian stimulation, recombinant FSH (or other products based on FSH) are given at the beginning of the follicular phase for an average of 10-12 days. The reason for this timing is mainly due to the fact that the follicular phase is clearly the moment when the ovaries are recruiting new follicles in order to establish the dominant for the cycle. However, as previously described follicular production by the ovaries follows a pattern of multicyclic waves. More specifically, a wave is a synchronous growth of follicles that have similar diameter and that can be documented with ultrasound . Beside the very well-known follicular wave (which is the one exploited in the COS), 64% of the women has two waves (follicular and luteal) and 32% of women has up to 3 waves in a normal cycle (early follicular, late follicular and luteal) .
The innovative concept of multiple waves of follicular development has been utilized in previous studies aiming to evaluate the effect of more than 1 stimulation cycles in a short period of time (less than 1 month). Specifically, two stimulation cycles have been performed in the same cycle by previous researcher (starting from the classical follicular COS and followed by a subsequent stimulation 5 days after the first oocyte retrieval) and it has been shown to be associated with improved cycle outcomes, alias higher number of oocytes retrieved and number of embryos obtained in total. Furthermore, in women with low ovarian response recent studies have suggested that the luteal phase stimulation appears to result in a higher number of oocytes retrieved as compared to the first follicular phase stimulation cycle .
Nevertheless, in spite of the accumulating evidence, a common characteristic of all of the published trials up to date is that in all of them dual stimulation cycle was initiated in the classical follicular phase followed by second stimulation cycle 5 days after oocytes retrieval. This approach had two major limitations:
- Owing to this extended protocol and the luteal phase start the lack of synchronization between embryos and endometrium, a freeze-only protocol was considered essential to be adopted .
- The fact that the 2nd stimulation cycle (luteal phase) always started 5 days after the first stimulation cycle does allow an unbiased evaluation of whether the improved outcomes on the second cycle are attributed to the luteal phase initiation of stimulation or to a carry-over effect of the first stimulation cycle.
Based on the above evidence we decided to design the current randomized trial which is, to our knowledge, the first to evaluate the benefit from the dual stimulation approach, not followed by a freeze-only strategy, but by fresh embryo transfer. In order to achieve this, we aim to compare the COS with the double stimulation (first luteal stimulation and then follicular ovarian stimulation) followed by fresh embryo transfer (ET) in poor prognosis patients undergoing in vitro fertilization/intra-cytoplasmatic sperm injections (IVF/ICSI) treatment.
The current randomized trial will allow us to
- compare the double stimulation with a single stimulation strategy followed by fresh embryo transfer and
- perform comparison of a luteal phase (1st cycle of the double stimulation group) and a follicular phase stimulation (control group) in a randomized setting
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double Stimulation (Elonva+rFSH) in luteal /follicular phase | Experimental | Drug: Double Stimulation (Elonva+rFSH) in luteal /follicular phaseA first stimulation Stimulation will initiate in the luteal phase of the menstrual cycle On day 21 of the previous cycle150mcg of corifollitropin alfa (Elonva, Merck Sharp \& Dohme (MSD), Spain) will be administrated and from day 8 of the stimulation when necessary, r-FSH of 250 IU per day will start until the day of ovulation trigger in a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol. The first ovulation triggering will be induced with GnRH-agonist (triptorelin 0.2 ml). The embryos obtained from the first stimulation will be cryopreserved in a freeze-all approach. A second stimulation will start on day 2 of bleeding after the first oocyte retrieval. This time will correspond to a conventional COS where corifollitropin alfa will be administered on the beginning of the follicular phase, in a flexible antagonist protocol, and the second ovulation will be triggered with 250μg of Recombinant Human Chorionic Gonadotropin (rhCG) |
| Conventional Stimulation (Elonva+rFSH) in follicular phase | Active comparator | Drug: Conventional Stimulation (Elonva+rFSH) in follicular phaseA conventional COS where Corifollitropin alfa will be administered on the beginning of the follicular phase, in a flexible antagonist protocol, and the second ovulation will be triggered with 250μg of rhCG |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Poor prognosis patients according to the POSEIDON group 3 \& 4 (based on AMH)
- AMH <1.2
- age <40 years old
- BMI >18 and <35 kg/m2
- Body weight >50kg (in women <36 years old body weight >60kg)
Key exclusion criteria (4 listed)
- Maternal age > 40 years
- History of untreated autoimmune, endocrine or metabolic disorders
- Previous ovarian cystectomy or oophorectomy
- Body weight <50kg (and body weight <60kg in women <36 years old)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Double Stimulation (Elonva+rFSH) in luteal /follicular phaseFollowing the 2nd oocyte retrieval, the patient will start luteal phase support (LPS) with vaginal micronized progesterone 200mg x 3 times a day until the day of the pregnancy test. All embryos will be cultured until day 5 in time-lapse incubators. In case of no blastocyst in the second cycle, or in case of poor embryo quality and in case of availability of frozen embryos from the first stimulation cycle, 1 frozen blastocyst from the first cycle will be thawed and will be transferred 5 days following the 2nd oocyte retrieval. Embryo transfer will be performed in all patients with available blastocysts, except in cases of high risk of ovarian hyperstimulation syndrome (OHSS) or progesterone elevation which is considered clinically relevant on the day of human chorionic gonadotropin (hCG) trigger, in which freeze-all strategy and deferred frozen embryo transferred will be considered. | Drug | Double Stimulation (Elonva+rFSH) in luteal /follicular phase |
| Conventional Stimulation (Elonva+rFSH) in follicular phaseFrom the day of oocyte retrieval, the patients will be asked to start the LPS with vaginal micronized progesterone 3 times a day until the day of the pregnancy test. Embryo transfer will be performed in all patients with available blastocysts, except in cases of high risk of OHSS or progesterone elevation which is considered clinically relevant on the day of hCG trigger, in which freeze-all strategy and deferred frozen embryo transferred will be considered. | Drug | Conventional Stimulation (Elonva+rFSH) in follicular phase |
Primary outcome
Number of good-quality blastocysts
Time frame: Day of embryo transfer (9 -20 days from initiation of the last ovarian stimulation)
Embryo quality will be assessed according to the Istanbul consensus workshop criteria (Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Human Reproduction 2011) and good quality embryo (GQE) at this developmental will be an expanded through to hatched blastocyst with an inner cell mass (ICM) that is prominent, easily discernible and consisting of many cells, with the cells compacted and tightly adhered together, and with a trophectoderm (TE) that comprises many cells forming a cohesive epithelium
10 secondary outcomes
Number oocytes retrieved
Time frame: 9 -20 days from initiation of the last ovarian stimulation
Number of cycles reaching the stage of embryo transfer
Time frame: 9 -20 days from initiation of the last ovarian stimulation
Clinical pregnancy
Time frame: 6-7 weeks of gestation
Ongoing pregnancy
Time frame: 8-10 weeks of gestation
Time to pregnancy
Time frame: 4-6 weeks of gestation
Number of oocytes between follicular phase or luteal phase initiation of ovarian stimulation
Time frame: 9 -20 days from initiation of the ovarian stimulation
Number of Metaphase II oocytes (MII) between follicular phase or luteal phase initiation of ovarian stimulation
Time frame: 9 -20 days from initiation of the ovarian stimulation
Total additional dose of recombinant follicle stimulating hormone (rFSH)
Time frame: 9 -20 days from initiation of the ovarian stimulation
Length of stimulation
Time frame: 9 -20 days from initiation of the ovarian stimulation
Endocrine profile
Time frame: Day 1, Day 6 , Day 8 of stimulation and Day of trigger 9 -20 days from initiation of the ovarian stimulation in each ovarian stimulation cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Background: PubMed 30795977Alsbjerg B, Haahr T, Elbaek HO, Laursen R, Povlsen BB, Humaidan P. Dual stimulation using corifollitropin alfa in 54 Bologna criteria poor ovarian responders - a case series. Reprod Biomed Online. 2019 May;38(5):677-682. doi: 10.1016/j.rbmo.2019.01.007. Epub 2019 Jan 22.
- Background: PubMed 21502182Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.
- Background: PubMed 12849812Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
- Background: PubMed 28837031Cardoso MCA, Evangelista A, Sartorio C, Vaz G, Werneck CLV, Guimaraes FM, Sa PG, Erthal MC. Can ovarian double-stimulation in the same menstrual cycle improve IVF outcomes? JBRA Assist Reprod. 2017 Sep 1;21(3):217-221. doi: 10.5935/1518-0557.20170042.
- Background: PubMed 28778278Coutifaris C. Freeze-only in vitro fertilization cycles for all? Fertil Steril. 2017 Aug;108(2):233-234. doi: 10.1016/j.fertnstert.2017.06.028. No abstract available.
- Background: PubMed 26724797Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, Polyzos NP. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016 Feb;31(2):370-6. doi: 10.1093/humrep/dev316. Epub 2016 Jan 2.
- Background: PubMed 21505041Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
- Background: PubMed 24161646Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.
- Background: PubMed 29030068Liu C, Jiang H, Zhang W, Yin H. Double ovarian stimulation during the follicular and luteal phase in women >/=38 years: a retrospective case-control study. Reprod Biomed Online. 2017 Dec;35(6):678-684. doi: 10.1016/j.rbmo.2017.08.019. Epub 2017 Aug 24.
- Background: PubMed 25311972Moffat R, Pirtea P, Gayet V, Wolf JP, Chapron C, de Ziegler D. Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited. Reprod Biomed Online. 2014 Dec;29(6):659-61. doi: 10.1016/j.rbmo.2014.08.010. Epub 2014 Sep 4.
- Background: PubMed 30010882Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT, Seli E. Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance. Hum Reprod. 2018 Aug 1;33(8):1489-1498. doi: 10.1093/humrep/dey238.
- Background: PubMed 24581984Polyzos NP, Nwoye M, Corona R, Blockeel C, Stoop D, Haentjens P, Camus M, Tournaye H. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014 Apr;28(4):469-74. doi: 10.1016/j.rbmo.2013.11.010. Epub 2013 Dec 4.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nikolaos P Polyzos, MD PhD study director
Hopital Universitari Dexeus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Double Stimulation (Elonva+rFSH) in luteal /follicular phase and Conventional Stimulation (Elonva+rFSH) in follicular phase in people with Infertility, run by Fundación Santiago Dexeus Font at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of good-quality blastocysts (time frame: Day of embryo transfer (9 -20 days from initiation of the last ovarian stimulation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04446845, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.