Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000824167
Ethics application status
Approved
Date submitted
30/05/2019
Date registered
7/06/2019
Date last updated
7/06/2019
Date data sharing statement initially provided
7/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of progesterone levels at oocyte retrieval and impact on pregnancy outcomes: a retrospective cohort study.
Scientific title
Evaluation of progesterone levels at oocyte retrieval and impact on pregnancy outcomes in women undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI): a retrospective cohort study
Secondary ID [1] 297809 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 312173 0
Condition category
Condition code
Reproductive Health and Childbirth 310722 310722 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Blood samples are routinely tested for hormonal changes during controlled ovarian stimulation for IVF/ICSI cycles. Progesterone levels at the time of oocyte retrieval, 36-38 hours after trigger, were assessed routinely. IVF/ICSI cycle outcomes were recorded and serum progesterone concentration used to determine the probability of ongoing pregnancy in women undergoing IVF/ICSI cycles. Observation duration is from oocyte retrieval to second trimester of pregnancy.
Intervention code [1] 314049 0
Not applicable
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319567 0
Clinical Pregnancy, The ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy.
Timepoint [1] 319567 0
Approximately 12 weeks during pregnancy cycle
Secondary outcome [1] 368688 0
Biochemical pregnancy assessed using beta hCG in maternal serum.
Timepoint [1] 368688 0
At time of the detection of beta hCG in maternal serum, 11-15 days after embryo transfer.

Eligibility
Key inclusion criteria
Females aged 18 years or older
Undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycle using fresh or frozen ejaculated sperm from a male partner or sperm donor.
Have serum progesterone recorded at the time of oocyte retrieval from the Fertility SA pathology laboratory.
Minimum age
18 Years
Maximum age
53 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Oocyte Donors
Women undergoing ovarian preservation for fertility preservation.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Due to the exploratory retrospective nature of the study it has been determined that all eligible cycles within the last 2 years would be utilised. Uncertainty around the effect estimates produced by this study will be communicated using 95% confidence intervals.

All continuous variables will be expressed as mean (standard deviation-SD) or as median (interquartile range-IQR) depending on the normality of their distribution, which will be evaluated by inspection of distribution plots and the Kolmogorov-Smirnov test. Categorical variables will be expressed as proportions or percentages.
Regarding the research question of interest and in accordance with the exploratory nature of the study, the following approaches will be undertaken:
a) Firstly, the association will be explored by using the variable “Progesterone at the time of OPU” as a continuous one. For this purpose, fractional polynomial regression models will be constructed which can account for non-linear associations of the continuous predictors.
b) Subsequently, the variable “Progesterone at the time of OPU will also be divided and quartiles and their association with ongoing pregnancy rates will also be explored.
c) Receiver operating characteristics analyses will also be undertaken and the area under the curve will be estimated. Similarly, for any predictive regression model, the c-statistic will be calculated.
Due to the clustered nature of data (some patients contributed more than one cycles) the analysis of the data will be performed with the use of generalized estimating equations (GEE), which is an extension of the generalised linear model framework and accounts for any auto-correlation (cluster effect) between the data. Depending on the continuous or binary nature of the dependent variable, linear and logit regression models will be used to extract results regarding potential associations. Potential confounders will be identified through bivariate regression analyses. These confounders will subsequently be entered as covariates in the multivariable regression models which will be constructed aiming to evaluate the association of interest.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/06/2019
Actual
Date of last participant enrolment
Anticipated
31/07/2019
Actual
Date of last data collection
Anticipated
31/07/2019
Actual
Sample size
Target
800
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 13484 0
St Andrew's Hospital Inc - Adelaide
Recruitment postcode(s) [1] 26103 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 302334 0
Commercial sector/Industry
Name [1] 302334 0
Ferring Pharmaceuticals Pty Ltd
Country [1] 302334 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Fertility SA
Address
Fertility SA,
Level 9, 431 King William Street,
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 302213 0
None
Name [1] 302213 0
Address [1] 302213 0
Country [1] 302213 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303007 0
St Andrews Human Research Ethics Committee
Ethics committee address [1] 303007 0
St Andrews Hospital,
350 South Terrace,
Adelaide, SA, 5000
Ethics committee country [1] 303007 0
Australia
Date submitted for ethics approval [1] 303007 0
Approval date [1] 303007 0
17/08/2018
Ethics approval number [1] 303007 0
Project Number #106

Summary
Brief summary
Elevated progesterone on the day of hCG administration has been associated with significantly lower pregnancy rates when a fresh embryo transfer occurs. Although evidence is available to support this notion, numerous contradictory studies also exist . Presently, many clinics practice minimal stimulation and/or “minimal intervention” cycles, where patients are managed externally, and therefore patient’s progesterone levels at the time of hCG are not monitored.
In 2014 Nayak et al demonstrated that elevated progesterone on the day of oocyte retrieval is associated with significantly lower implantaton and ongoing pregnancy rates. Implantation and pregnancy rates were significantly higher when the progesterone level was less than 12 ng/mL on the day of oocyte retrieval. Furthermore, miscarriage rates were higher when the P level was greater than or equal to 12 ng/mL, although this did not reach statistical significance.
Premature progesterone elevation is believed to negatively impact endometrial receptivity however, premature progesterone rise has also been shown to have no effect on oocyte/embryo quality. Peripheral progesterone in the late follicular phase is likely to influence endometrial maturation. Endometrial samples exposed to low and high concentrations progesterone on the day of HCG administration had significantly different gene expression. These observations could explain the impairment of endometrial receptivity in the presence of elevated progesterone. Some reports discuss measures to prevent a premature progesterone rise, however once the progesterone rise has occurred then the optimal solution is to vitrify all embryos and transfer in a natural cycle. This method is supported by the fact that embryos obtained from cycles with an elevated progesterone and transferred into endometrium unaffected by elevated progesterone do not result in impaired pregnancy rates in either frozen-thawed or donor/recipients.
Therefore, by evaluating progesterone levels at a time more proximal to embryo transfer, when patients must be in attendance with fertility staff, premature progesterone elevation could be identified so patient treatment could be modified to improve the chances of a successful pregnancy.
Primary Objective: To determine the impact of serum progesterone concentration on the day of OPU on the probability of ongoing pregnancy in women undergoing IVF/ICSI.
Secondary Objectives: To determine a progesterone cut-off value at oocyte retrieval that has the best capacity to discriminate between cycles that do and those that do not result in an ongoing pregnancy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92146 0
Dr Ryan Rose
Address 92146 0
Fertility SA,
St Andrews Hospital,
350 South Terrace,
Adelaide, SA, 5000
Country 92146 0
Australia
Phone 92146 0
+61 08 8100 2916
Fax 92146 0
Email 92146 0
[email protected]
Contact person for public queries
Name 92147 0
Dr Ryan Rose
Address 92147 0
Fertility SA,
St Andrews Hospital,
350 South Terrace,
Adelaide, SA, 5000
Country 92147 0
Australia
Phone 92147 0
+61 08 8100 2916
Fax 92147 0
Email 92147 0
[email protected]
Contact person for scientific queries
Name 92148 0
Dr Ryan Rose
Address 92148 0
Fertility SA,
St Andrews Hospital,
350 South Terrace,
Adelaide, SA, 5000
Country 92148 0
Australia
Phone 92148 0
+61 08 8100 2916
Fax 92148 0
Email 92148 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.