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. 2021 Mar 18;2021(3):CD011424. doi: 10.1002/14651858.CD011424.pub3

Parsanezhad 2013.

Study characteristics
Methods Randomised controlled trial, 2 groups, set in Shiraz University Infertility Clinic, Iran
January 2010 to March 2012
Number of participants randomised: 234
Number of participants analysed: 217
Participants Inclusion criteria: unexplained infertility: normal ovulatory function, normal uterine cavity, bilateral tubal patency via hysterosalpingography and/or hysterolaparoscopy if indicated;
women between 23 and 35 years of age; infertility duration 2 to 5 years; body mass index 18 to 25 kg/m²; anti‐mullerian hormone > 1 µg/L; follicle‐stimulating hormone < 10 mlU/mL on third day of the cycle; ≥ 10 to 12 follicles in antral follicle count; received clomiphene citrate for infertility only during the past 3 months and no previous treatment with gonadotropins or any other interventions for treatment of infertility; men: normal semen analysis parameters (as defined by World Health Organization criteria)
Exclusion criteria: other known infertility etiologies such as hormonal disorders, infections, genetic anomalies, immunological problems, and abnormal anatomic structures; painters, factory workers; smoking; alcohol abuse
Cause of subfertility: unexplained infertility
Interventions
  • Intervention group: mild endometrial local injury in the posterior wall of the uterus by standard pipelle endometrial sampling during preovulatory days (days of detecting urinary luteinising hormone surge)

  • Control group: gynaecological examination with a mock pipelle biopsy without any endometrial manipulation (no entry of pipelle into internal os of cervix)


Both groups: optimal superovulation by clomiphene citrate and regular timed intercourse (from luteinising hormone‐positive days until 8 days later every other day)
Degree of endometrial injury: pipelle
Timing of endometrial injury: follicular phase (days of detecting luteinising hormone surge, of a potential conception cycle)
Study length: unclear in the paper; quote from author correspondence: "about 3 menstrual cycles"
Type of conception: regularly timed intercourse
Control group was administered a mock procedure, which was not intended to cause injury but is likely to have done so; this may be considered an inappropriate control procedure (pipelle inserted through external but not internal os)
Outcomes Reported in the paper:
  • Clinical pregnancy (human chorionic gonadotropin test after 1 week, missed period + transvaginal sonography at 6 to 7 weeks' gestation)

  • Abortion rate (miscarriage by 20 weeks' gestation)

  • Ongoing pregnancy (pregnancy after 20 weeks' gestation)


Obtained by author correspondence:
  • Confirmed live birth rate same as ongoing pregnancy rate (no miscarriages after 20 weeks)

Notes Funding source: Infertility Research Center of Shiraz University
Conflicts of interest: study authors reported none
Trial registration number: IRCT2012082510657N1 (retrospectively registered)
Author correspondence was undertaken but was incomplete
Although study authors report Parsanezhad 2013 and Dadras 2012 to be distinct studies, it is unclear how both were conducted at the same centre, in overlapping time periods, and reported by overlapping authors. For this and other reasons, we excluded Dadras 2012 from the review
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote from author correspondence: "allocation proceeded by randomly selecting one of the orderings and assigning the next block of participants to study groups according to the specified sequence"
It is unclear how these sequences were generated, and whether this was truly random. From author correspondence, it appears that data from some participants enrolled at the beginning of the study period may have been removed from analysis to reduce any inter‐investigator discrepancies at the changeover of the study gynaecologists
Allocation concealment (selection bias) High risk Not reported in the paper
Quote from author correspondence: "since we chose each block size of 2, there were 2 possible ways to equally assign participants to a block (AB or BA)"
A block size of 2 means every second allocation is known; therefore this is a high‐risk method
Blinding of participants (performance bias) Unclear risk Use of a sham procedure (mock pipelle biopsy, insertion of pipelle into external but not internal os) reported in the paper and confirmed in author correspondence; however, there is no mention of a placebo procedure in the trial register, and there was no assessment of whether participants were truly blinded by the placebo procedure
Blinding of personnel (performance bias) High risk Study authors did not report any blinding of personnel
Blinding of outcome assessment (detection bias)
All outcomes Low risk Study authors did not report blinding of outcome assessors, and it was unlikely; however outcomes were unlikely to be influenced by lack of blinding
Incomplete outcome data (attrition bias)
All outcomes Low risk Number of missing outcome data: 17 (3 in the intervention group, 14 in the control group). Reasons for missing outcome data were reported. The proportion of missing outcomes compared with observed event risk was not enough to have a significant impact on the intervention effect estimate
Selective reporting (reporting bias) Unclear risk Retrospective registration on Iranian registry of clinical trials. IRCT2012082510657N1
Methods in the registered trial do not entirely match the methods in the full report. However, all expected outcomes are reported. Study authors provided live birth rates and stated that pain was not recorded
Other bias Low risk We did not identify any other sources of bias