A Proof of Concept Study of Serum Progesterone Levels for IVF/ICSI Following HCG Trigger for Oocyte Maturation

Infertility Clinical Trial

Official title:

A Proof of Concept Study to Determine the Rise of Progesterone Levels After Human Chorionic Gonadotrophin (hCG) Trigger in Stimulated Cycles of IVF/ICSI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04417569
• Other study ID #: 2002-ABU-001-CC
• Status: Completed
• Start date: February 4, 2021
• Est. completion date: June 30, 2021

Study information

• Verified date: February 2022
• Source: ART Fertility Clinics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will determine the rise of progesterone levels after human chorionic gonadotrophin (hCG) trigger in stimulated cycles IVF/ICSI

Description:

Studies have suggested that controlled ovarian hyperstimulation adversely affects endometrial receptivity. In ovarian stimulation cycles with exogenous gonadotrophins there is an ongoing debate regarding the effect of a late follicular phase progesterone level on reproductive outcomes. It is not yet clarified if an elevated serum progesterone level in the late follicular phase is a symptom or cause of an adverse effect on reproductive outcomes. A new hypothesis is evolving and gaining momentum providing a novel explanation for the association between late follicular phase progesterone rise and reproductive outcome. It is proposed that exogenous FSH (Follicle-stimulating hormone) administration results in supraphysiological levels of FSH, which induce an abundance of LH (luteinizing hormone) receptors on granulosa cells causing the follicles to become hypersensitive to LH-like activity (ie hCG trigger). Based on this hypothesis, the focus should be placed on the hCG trigger rather than on the late follicular phase progesterone rise.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 30, 2021
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

Inclusion Criteria:

• Females aged 18 to 42 years with regular menstrual cycles of 26-34 days

• Undergoing ovarian stimulation for IVF/ICSI & PGS.

• Receiving recombinant FSH for stimulation

• hCG 5000iu IM as trigger injection for oocyte maturation.

• Ovarian stimulation in GnRH-antagonist protocols

• BMI 18- 35 kg/m2

• Having 1 or 2 euploid embryos for transfer in spontaneous natural cycles.

Exclusion Criteria:

• Poor ovarian reserve as defined by Bologna criteria

• PCOS in accordance with Rotterdam criteria

Related Conditions & MeSH terms

• hCG
• Infertility
• Infertility, Female
• IVF

Intervention

Drug:
• hCG
human chorionic gonadotropin

Diagnostic Test:
• Ultrasound
Endometrial thickness monitoring

Other:
• Blood test
Progesterone, Luteinizing Hormone, Estradiol

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (20)

Bosch E, Labarta E, Crespo J, Simón C, Remohí J, Jenkins J, Pellicer A. Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization: analysis of over 4000 cycles. Hum Reprod. 2010 Aug;25( — View Citation

Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. Review. — View Citation

Devroey P, Bourgain C, Macklon NS, Fauser BC. Reproductive biology and IVF: ovarian stimulation and endometrial receptivity. Trends Endocrinol Metab. 2004 Mar;15(2):84-90. Review. — View Citation

Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: — View Citation

Friis Wang N, Skouby SO, Humaidan P, Andersen CY. Response to ovulation trigger is correlated to late follicular phase progesterone levels: A hypothesis explaining reduced reproductive outcomes caused by increased late follicular progesterone rise. Hum Re — View Citation

Griesinger G, Mannaerts B, Andersen CY, Witjes H, Kolibianakis EM, Gordon K. Progesterone elevation does not compromise pregnancy rates in high responders: a pooled analysis of in vitro fertilization patients treated with recombinant follicle-stimulating — View Citation

Groenewoud ER, Macklon NS, Cohlen BJ; ANTARCTICA Study Group. The effect of elevated progesterone levels before HCG triggering in modified natural cycle frozen-thawed embryo transfer cycles. Reprod Biomed Online. 2017 May;34(5):546-554. doi: 10.1016/j.rbm — View Citation

Haas J, Smith R, Zilberberg E, Nayot D, Meriano J, Barzilay E, Casper RF. Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers. Fertil Steril. 2019 Sep;112(3):503-5 — View Citation

Haouzi D, Assou S, Mahmoud K, Tondeur S, Rème T, Hedon B, De Vos J, Hamamah S. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum Reprod. 2009 Jun;24(6):1436-45. doi: 10.10 — View Citation

Irani M, Robles A, Gunnala V, Reichman D, Rosenwaks Z. Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers. J Ovarian Res. 2017 Oct 16;10(1):70. doi: 10.1186/s13048-017-0367-7. — View Citation

Kolibianakis E, Bourgain C, Albano C, Osmanagaoglu K, Smitz J, Van Steirteghem A, Devroey P. Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endom — View Citation

Liu Y, Lee KF, Ng EH, Yeung WS, Ho PC. Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles. Fertil Steril. 2008 Dec;90(6):2152-64. doi: 10.1016/j.fertnstert.2007.10.020. Epub 2008 Jan 14. — View Citation

Nikas G, Develioglu OH, Toner JP, Jones HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod. 1999 Mar;14(3):787-92. — View Citation

Roque M, Lattes K, Serra S, Solà I, Geber S, Carreras R, Checa MA. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril. 2013 Jan;99(1):156-162. doi: 10.1016/j.fertnster — View Citation

Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Freeze-all policy: fresh vs. frozen-thawed embryo transfer. Fertil Steril. 2015 May;103(5):1190-3. doi: 10.1016/j.fertnstert.2015.01.045. Epub 2015 Mar 4. — View Citation

Simón C, Garcia Velasco JJ, Valbuena D, Peinado JA, Moreno C, Remohí J, Pellicer A. Increasing uterine receptivity by decreasing estradiol levels during the preimplantation period in high responders with the use of a follicle-stimulating hormone step-down — View Citation

Testart J, Frydman R, Feinstein MC, Thebault A, Roger M, Scholler R. Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise. Fertil Steril. 1981 Jul;36( — View Citation

Venetis CA, Kolibianakis EM, Bosdou JK, Tarlatzis BC. Progesterone elevation and probability of pregnancy after IVF: a systematic review and meta-analysis of over 60 000 cycles. Hum Reprod Update. 2013 Sep-Oct;19(5):433-57. doi: 10.1093/humupd/dmt014. Epu — View Citation

Weinerman R, Mainigi M. Why we should transfer frozen instead of fresh embryos: the translational rationale. Fertil Steril. 2014 Jul;102(1):10-8. doi: 10.1016/j.fertnstert.2014.05.019. Epub 2014 Jun 2. Review. — View Citation

Yding Andersen C, Bungum L, Nyboe Andersen A, Humaidan P. Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate. Reprod Biomed Online. 2011 Aug;23(2):187-95. doi: 10.1016/j.rbmo. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Level of progesterone day of trigger	day of the hCG trigger between 1000h - 1200h, before trigger, 1 hour after trigger, 2 hrs after trigger	1 day
Secondary	Level of progesterone day of egg retrieval	36hrs after trigger	1 day