Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Cetrorelix

   human RCT Direct outcome Approved for this condition

   Who was studied

   women undergoing controlled ovarian stimulation for IVF or ICSI; Cochrane pooled 73 RCTs, n=12,212, of which 44 trials used cetrorelix; the live birth analysis rests on 12 RCTs, n=2,303

   FDA-approved indication is "inhibition of premature LH surges in women undergoing controlled ovarian stimulation" — a single mechanical step inside an assisted reproduction cycle, not a treatment for infertility. Pooled across RCTs, live birth rate did not differ from the long-course GnRH agonist protocol (OR 1.02, 95% CI 0.85 to 1.23) while ovarian hyperstimulation syndrome was less frequent (OR 0.61, 95% CI 0.51 to 0.72); the drug is what allows the cycle to run to a planned trigger, and no trial tested it as a fertility treatment on its own.

   Source PubMed Central 2 primary sources read for this row

2. Ganirelix

   human RCT Direct outcome Approved for this condition

   Who was studied

   women undergoing controlled ovarian hyperstimulation for IVF or ICSI; Cochrane pooled 73 RCTs, n=12,212, of which 19 trials used ganirelix; registrational open-label study n=463, mean 5.4 days of treatment

   FDA-approved indication is "inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation" — an adjunct that protects one step of an assisted reproduction cycle rather than a treatment for infertility. The registrational endpoint was the incidence of a premature LH surge (under 1% of 463 subjects), which is a process measure, not a pregnancy; the live birth comparison against the long agonist protocol comes from the Cochrane pooled analysis (OR 1.02, 95% CI 0.85 to 1.23) and shows no difference.

   Source PubMed Central 2 primary sources read for this row

3. Leuprolide

   human RCT Direct outcome Off-label use

   Who was studied

   women in GnRH-antagonist IVF/ICSI cycles; Cochrane review 17 RCTs, n=1,847, of which the fresh autologous live birth analysis covers 5 RCTs, n=532

   Leuprolide's approved indications are advanced prostate cancer, endometriosis, uterine fibroids and central precocious puberty; use for pituitary downregulation or as an alternative trigger inside an assisted reproduction cycle is off-label, and is a step in a cycle rather than a treatment for infertility. Used as the trigger in fresh autologous cycles it was associated with a lower live birth rate than hCG (OR 0.47, 95% CI 0.31 to 0.70), with less ovarian hyperstimulation syndrome.

   Source PubMed 2 primary sources read for this row

4. hCG

   human RCT Surrogate marker Approved for this condition

   Who was studied

   infertile women pretreated with FSH after pituitary desensitisation in an IVF and embryo transfer programme; pivotal randomised study n=94 receiving choriogonadotropin alfa 250 mcg

   FDA-approved (Ovidrel) for "the induction of final follicular maturation and early luteinization" in women already in an ART programme — that is the trigger step of a cycle, not a treatment for infertility. The pivotal trial's primary endpoint was the number of oocytes retrieved (mean 13.6), a surrogate; clinical pregnancy per initiated cycle (35.1%) was secondary and the trial was designed to show equivalence to urinary hCG, not to measure live birth.

   Source DailyMed — the FDA label 1 primary source read for this row

5. Gonadorelin

   human observational Direct outcome Not approved for this condition

   Who was studied

   women aged 20–40 with functional hypothalamic amenorrhoea, n=66, 82 treatments and 212 ovulation induction cycles, 1996–2020; subcutaneous pulsatile gonadorelin 10 mcg every 90 minutes by pump

   This is pulsatile ovulation induction outside assisted reproduction, not an adjunct within an IVF cycle: a retrospective single-centre cohort reported a cumulative live birth rate of 65.9% per treatment and 96% ovulation per cycle in functional hypothalamic amenorrhoea. No gonadorelin product currently marketed in the US carries an approval for use in assisted reproduction, and the cohort is uncontrolled, so the rate cannot be read as an effect size.

   Source PubMed Central 1 primary source read for this row

Checked, and nothing recorded

2 compounds were checked against assisted reproduction and produced no gradeable row.

• GnRH (Gonadotropin-Releasing Hormone) — checked, no row on file
• Kisspeptin-10 — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.