Video summary

Fertility Masterclass 13 - PCOS Stimulation in non IVF Cycles | PCOS Stimulation Protocol

Main summary

Key takeaways

Educational

Main Ideas & Lessons Conveyed

Core pathophysiology to understand PCOS stimulation (the “only mechanism” focus)

  • PCOS stimulation is driven primarily by insulin resistance → compensatory hyperinsulinemia.
  • Excess insulin alters ovarian signaling:
    • When insulin is normal: the tyrosine pathway supports normal hormone production.
    • With excess insulin: the serin pathway shifts the ovary toward increased androgen production.
  • PCOS also involves altered LH excess (LH/androgen dysregulation), contributing to an androgenic ovarian microenvironment.
  • This leads to:
    • Chronic anovulation
    • Infertility
  • Follicle behavior:
    • Pattern of daily recruitment + simultaneous atresia/apoptosis, producing the ultrasound impression of multiple follicles.

Overall clinical goal in non-IVF cycles

In natural intercourse / timed intercourse and IUI, the aim is controlled follicular development:

  • Thin patients (lean PCOS framing): target 1–2 follicles
  • IUI (and obesity PCOS framing also addressed): target ~3 follicles

Medication principles emphasized

  • Letrozole (LOL) is presented as the “drug of choice” for:
    • Natural intercourse in PCOS
    • IUI in PCOS
  • Clomiphene citrate is stated to no longer be the drug of choice (per speaker guidance).
  • Emphasis: avoid overthinking/over-adjusting protocol-by-protocol unless there is documented failure.

Standard stimulation protocol (4-part session structure)

The session is divided into four categories, primarily built around:

  1. PCOS with natural intercourse
  2. PCOS with IUI
  3. Management when the standard protocol fails
  4. Adjuncts/trigger/luteal support and cycle management principles

Detailed Protocol / Instruction List (as stated)

A) Targets & categorization

  • Natural intercourse (lean/thin PCOS framing)
    • Target: 1–2 follicles
  • IUI (and obesity PCOS framing)
    • Target: ~3 follicles

B) Drug of choice

For all categories (natural intercourse and IUI):

  • Letrozole (LOL) is the preferred medication.

C) Standard letrozole dosing (routine protocol)

  • Thin/lean PCOS
    • Letrozole 2.5 mg once daily for 5 days
    • Target: 1–2 follicles
  • IUI
    • Letrozole 2.5 mg twice daily for 5 days
    • Add HMG may be used
  • Obese PCOS
    • Letrozole 2.5 mg twice daily for 5 days
    • Speaker reiterates a similar continuing pattern (“2.5 again twice a day for five”)
    • Add HMG is emphasized

Note: The summary mentions some wording ambiguity in the thin/lean portion, but overall guidance centers on the 2.5 mg starting concept for routine patterns.

D) Role of HMG (human menopausal gonadotropin)

  • HMG addition is emphasized as important for recruitment, especially because recruitment is described as happening largely in the first ~5 days.
  • Standard HMG dose (when added):
    • 150 IU HMG
  • Alternative view mentioned:
    • Recombinant FSH can be used, but the speaker prefers HMG standardization due to the belief that endogenous LH is abnormal in PCOS, and HMG may help mitigate the impact of abnormal LH.

E) When the standard protocol fails

  • Failure definition: after 3–4 cycles of standard LOL ± HMG with failure, including:
    • Patient has tried multiple cycles and failed
    • Patient comes after changing doctors (several failed attempts)
  • Next step: “Extended letrozole (extended LOL)”
    • Letrozole 2.5 mg twice daily for 8–10 days
  • Adjuncts during failure
    • HMG: may add when necessary
    • Low-dose HCG: may add when necessary (not emphasized as mandatory)

F) Use of insulin-sensitizers and steroids

  • Metformin
    • Beneficial in PCOS, especially obese PCOS
    • If used, it is continued throughout the cycle
  • Inositols (D-chiro-inositol / myo-inositol)
    • Speaker states no established role in increasing insulin sensitivity (used as justification for not recommending it here)
  • Steroids
    • If adding steroids:
      • Vigolone (prednisolone-like steroid; speaker uses “violone”) 5 mg at night
    • In routine protocol: not recommended
    • In protocol failures: may consider
    • Steroid continued throughout the cycle

G) Trigger (for non-IVF stimulation including IUI)

  • Trigger is stated as fixed:
    • hCG trigger 10,000 IU
  • Speaker emphasizes:
    • No agonist trigger for IUI cycles
    • No individualization—“no questions/doubts” should alter it

H) Luteal phase support (LPS)

After trigger:

  • Progesterone gel 8%
  • Either once daily or twice daily (either acceptable)
  • Rationale emphasized:
    • PCOS is framed as having abnormal LH, and standard LPS support is needed.

I) Duration/continuation of adjuncts and drugs (cycle timing)

  • Letrozole
    • Routine: shorter duration
    • Extended protocol: 8–10 days
  • Metformin: continuous (through the cycle)
  • Steroid: continuous (through the cycle)
  • HMG:
    • Typically only first ~5 days
    • If needed later, can add for additional 3–4 days
  • Possible antagonist mention:
    • “You may add antagonist based on requirements” (discussed in Q&A; not detailed as a main protocol step)

Q&A Highlights (additional clinical decisions emphasized)

  • Risk of OHSS / multiple pregnancy
    • With the described approach—especially keeping target follicles 1–2 (or ~3)—the speaker states OHSS risk is very rare.
    • Speaker reassurance: 150 IU HMG won’t cause OHSS (as stated).
  • Thin endometrium / estrogen
    • Mentioned conceptually; detailed estrogen protocol is not provided (speaker refers to other lectures).
  • CC + letrozole
    • Mentioned as supported only in studies, not routine practice.
  • LH monitoring / LH levels
    • Speaker discourages routine LH-value-based decisions due to:
      • PCOS having abnormal LH pulses
      • LH measurements potentially misleading
  • AMH (OM in subtitles)
    • Rule-of-thumb: AMH > 10 as a warning for hyperresponse or poor oocyte quality.
  • Switching/abandoning IUI/natural cycles
    • If no response after about 7 days of HMG starting day 2 (day 2 to day 9) → resistant ovary.
    • If recruitment is excessive after ~5–7 days, approach conceptually changes (less detailed).
  • When to convert to IVF
    • Speaker reports very few conversions recently (example: one patient in last year), emphasizing that proper stimulation should reduce surprises.
  • Ovarian drilling / laparoscopy
    • Not routine; potentially considered in highly resistant cases after repeated failures.
  • Step-up letrozole
    • Mentioned as a possible IUI strategy for multifollicular recruitment.
    • Warns against extending too long due to thin endometrium risk.
    • Example schedule:
      • 2 days 2.5 mg → 2 days 5 mg → 1 day 7.5 mg
    • Variations may exist.

Key “Take-Home” Flow (condensed)

  • Understand PCOS stimulation mechanism as: insulin resistance → hyperinsulinemia → androgenic microenvironment + altered LH excess → recruitment + apoptosis → chronic anovulation/infertility

  • For non-IVF:

    • Use letrozole with target follicle numbers
    • Add HMG 150 IU (especially to improve recruitment)
    • If failure after 3–4 cycles:
      • extend letrozole (2.5 mg BID for 8–10 days)
      • consider HMG/low-dose HCG when necessary
    • Consider metformin (especially obese PCOS)
    • Consider steroids (vigolone 5 mg at night) mainly for protocol failures
    • Trigger: hCG 10,000 IU
    • Luteal support: progesterone gel 8% after trigger
    • Continue metformin/steroid throughout the cycle; HMG mainly early

Speakers / Sources Featured

  1. Dr J Meta (main instructor; referred to as “Dr J meta”)
  2. Shilpa Madam (host/organizer; thanked and referenced for topic requests)
  3. “Sha Madam” / “Shilpa Madam” (appears to be the same person; used as “sha Madam” in subtitles)
  4. No other named external sources (no studies/authors cited explicitly in subtitles)

Original video