Clinical trial NCT02975713: Progesterone Diurnal Rhythm During Ovarian Stimulation for IVF
Official title: Progesterone Diurnal Rhythm During Ovarian Stimulation for IVF
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Ovarian Hyperstimulation
Keywords: P4,ART,IVF,FSH,LH,AMH
Lead sponsor: ART Fertility Clinics LLC
Sponsor class: OTHER
First posted: 2016-11-29
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have to undergo IVF due to primary or secondary infertility.

Brief summary: To evaluate the influence of circadian rhythm on progesterone levels during follicular phase of natural cycle and during follicular phase of controlled ovarian stimulation during IVF.

Detailed description: The primary aim of this study is to determine the circadian rhythm of progesterone in a stimulated cycle. Sample size calculations show that the study needs to recruit 10 women to show any significant differences in progesterone secreted in the morning at 8 am compared to that secreted in the evening at 8 pm. We have increased the number of participants to 12 in order to compensate for any possible drop outs. The hormones FSH, LH, Progesterone and Estradiol will be measured at days 2/3, 8, 10 and 12 of a normal and stimulated cycle so that each patient serves as her own control.

This study will provide the basis to establish the optimal blood sampling time for progesterone measurement and to more accurately determine the cut-off level for progesterone for favourable pregnancy outcomes in ART.

Eligibility criteria: Inclusion Criteria:

* Indication for IVF / ICSI - treatment
* Age ≥ 18 years and ≤ 35 years
* Ovarian reserve parameters in the adequate age - range, determined by Anti-Mullerian-Hormone (AMH) and Antral Follicle Count (AFC)(16)
* Able to understand the aim of the study and to provide consent
* Regular cycle (25-35 days)

Exclusion Criteria:

* Diagnosis of polycystic ovarian syndrome (PCOS) Rotterdam criteria
* Endometriosis stage 3 or 4 AFS
* Treatment with GnRH-analogues during the previous 6 months
* Intake of oral contraceptive pill (OCP) or any hormonal treatment during the last 3 months

Primary outcomes:
measure: Progesterone levels during follicular phase
timeFrame: 2-4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Abu Dhabi
country: United Arab Emirates
facility: IVI Middle East Fertilty Clinic
Study officials:
affiliation: IVI Middle East Clinic
name: Human Mo Fatemi, Medical Director
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fatemi HM, Van Vaerenbergh I. Significance of premature progesterone rise in IVF. Curr Opin Obstet Gynecol. 2015 Jun;27(3):242-8. doi: 10.1097/GCO.0000000000000172.
citation: Patton PE, Lim JY, Hickok LR, Kettel LM, Larson JM, Pau KY. Precision of progesterone measurements with the use of automated immunoassay analyzers and the impact on clinical decisions for in vitro fertilization. Fertil Steril. 2014 Jun;101(6):1629-36. doi: 10.1016/j.fertnstert.2014.02.037. Epub 2014 Mar 21.
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. Epub 2013 Jul 4.
citation: Huang R, Fang C, Xu S, Yi Y, Liang X. Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles. Fertil Steril. 2012 Sep;98(3):664-670.e2. doi: 10.1016/j.fertnstert.2012.05.024. Epub 2012 Jun 15.
citation: Ochsenkuhn R, Arzberger A, von Schonfeldt V, Gallwas J, Rogenhofer N, Crispin A, Thaler CJ, Noss U. Subtle progesterone rise on the day of human chorionic gonadotropin administration is associated with lower live birth rates in women undergoing assisted reproductive technology: a retrospective study with 2,555 fresh embryo transfers. Fertil Steril. 2012 Aug;98(2):347-54. doi: 10.1016/j.fertnstert.2012.04.041. Epub 2012 May 24.
citation: Xu B, Li Z, Zhang H, Jin L, Li Y, Ai J, Zhu G. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril. 2012 Jun;97(6):1321-7.e1-4. doi: 10.1016/j.fertnstert.2012.03.014. Epub 2012 Apr 10.
citation: Labarta E, Martinez-Conejero JA, Alama P, Horcajadas JA, Pellicer A, Simon C, Bosch E. Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25. doi: 10.1093/humrep/der126. Epub 2011 May 2.
citation: Van Vaerenbergh I, Fatemi HM, Blockeel C, Van Lommel L, In't Veld P, Schuit F, Kolibianakis EM, Devroey P, Bourgain C. Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression. Reprod Biomed Online. 2011 Mar;22(3):263-71. doi: 10.1016/j.rbmo.2010.11.002. Epub 2010 Nov 13.
citation: Bosch E, Labarta E, Crespo J, Simon C, Remohi 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(8):2092-100. doi: 10.1093/humrep/deq125. Epub 2010 Jun 10.
citation: Kyrou D, Popovic-Todorovic B, Fatemi HM, Bourgain C, Haentjens P, Van Landuyt L, Devroey P. Does the estradiol level on the day of human chorionic gonadotrophin administration have an impact on pregnancy rates in patients treated with rec-FSH/GnRH antagonist? Hum Reprod. 2009 Nov;24(11):2902-9. doi: 10.1093/humrep/dep290. Epub 2009 Aug 11.
citation: Strott CA, Yoshimi T, Lipsett MB. Plasma progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia. J Clin Invest. 1969 May;48(5):930-9. doi: 10.1172/JCI106052.
citation: Bungum L, Jacobsson AK, Rosen F, Becker C, Yding Andersen C, Guner N, Giwercman A. Circadian variation in concentration of anti-Mullerian hormone in regularly menstruating females: relation to age, gonadotrophin and sex steroid levels. Hum Reprod. 2011 Mar;26(3):678-84. doi: 10.1093/humrep/deq380. Epub 2011 Jan 11.
citation: Bungum L, Franssohn F, Bungum M, Humaidan P, Giwercman A. The circadian variation in Anti-Mullerian hormone in patients with polycystic ovary syndrome differs significantly from normally ovulating women. PLoS One. 2013 Sep 4;8(9):e68223. doi: 10.1371/journal.pone.0068223. eCollection 2013.
citation: Seifer DB, Baker VL, Leader B. Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States. Fertil Steril. 2011 Feb;95(2):747-50. doi: 10.1016/j.fertnstert.2010.10.011. Epub 2010 Nov 13.