Can I increase oral micronized progesterone to 200 mg three times daily at 10 days post‑LH surge while trying to conceive, given a prior miscarriage on twice‑daily dosing, thin endometrium after letrozole 7.5 mg from cycle day 3‑7, and current metformin 500 mg twice daily?

Progesterone Supplementation for Recurrent Pregnancy Loss

You should continue your current twice-daily progesterone dosing (200 mg twice daily) rather than increasing to three times daily, as there is no evidence that higher doses improve pregnancy outcomes in your situation, and the standard evidence-based regimen for women with prior miscarriage and early pregnancy bleeding is 400 mg total daily (200 mg twice daily). 1

Evidence-Based Dosing for Your Situation

Your clinical scenario involves trying to conceive with a history of recurrent pregnancy loss, which requires specific progesterone supplementation guidance:

• The established effective dose is 200 mg vaginal micronized progesterone twice daily (400 mg total daily), which has been validated in large randomized trials specifically for women with prior miscarriage(s). 1

• The landmark PRISM trial studied 4,153 women and found that 400 mg daily (given as 200 mg twice daily) significantly improved live birth rates in women with both prior miscarriage and early pregnancy bleeding (75% vs 70% with placebo, P=0.003). 1

• For women with 3 or more previous miscarriages and current pregnancy bleeding, this same 400 mg daily dose showed even greater benefit (72% vs 57% live birth rate, P=0.004). 1

Why Not Increase to Three Times Daily?

There is no clinical trial evidence supporting 600 mg daily (200 mg three times daily) for miscarriage prevention. The studies establishing progesterone's efficacy used 400 mg daily maximum:

• All major trials demonstrating benefit used either 200 mg daily or 400 mg daily dosing regimens. 1

• One study examining 200 mg three times daily (600 mg total) was conducted in the IVF luteal phase support context, not for recurrent pregnancy loss prevention. 2

• Higher doses do not necessarily provide better endometrial protection or pregnancy outcomes, and the evidence base stops at 400 mg daily for your indication. 3, 1

Timing Considerations Critical to Your Plan

You should start progesterone supplementation immediately when pregnancy is confirmed, not wait until 10 days post-LH surge while trying to conceive:

• Progesterone's beneficial effects occur when started early in pregnancy, particularly before 9 weeks gestation. 4

• The protective effect is complete by 12 weeks of pregnancy, when the placenta takes over progesterone production. 4

• Starting progesterone before pregnancy confirmation (at 10 days post-ovulation while still trying to conceive) has no established benefit and is not part of evidence-based protocols. 1

Addressing Your Letrozole and Endometrial Concerns

Your concern about thin endometrium from letrozole 7.5 mg is valid, but increasing progesterone dose is not the solution:

• Progesterone supports the endometrium after ovulation and implantation, but excessive progesterone does not compensate for inadequate estrogen-driven endometrial proliferation. 3

• If endometrial thickness is truly inadequate (typically <7 mm at ovulation), this should be addressed by adjusting your letrozole dose or adding estrogen supplementation, not by increasing progesterone. 5

• Your metformin 500 mg twice daily is appropriate for metabolic support but does not directly affect progesterone requirements. 1

Recommended Protocol for Your Next Cycle

Follow this specific algorithm:

1. Continue letrozole as prescribed (though consider discussing endometrial monitoring with your physician if thickness is truly concerning)

2. Obtain a sensitive pregnancy test starting 12-14 days post-LH surge

3. If pregnancy test is positive, immediately start vaginal micronized progesterone 200 mg twice daily (morning and evening)

4. Continue progesterone through 12 weeks of gestation (not 16 weeks, as the beneficial effect is complete by 12 weeks and prolonged exposure has theoretical but uncertain risks to offspring) 4

5. Do not increase to three times daily dosing, as this exceeds evidence-based protocols without demonstrated additional benefit 1

Important Safety Considerations

• The PROMISE and PRISM trials found no short-term safety concerns with 400 mg daily vaginal progesterone in early pregnancy. 1

• Vaginal administration is preferred over oral for pregnancy support due to better local endometrial effects and fewer systemic side effects. 3, 1

• Taking progesterone at bedtime can minimize the mild drowsiness that some women experience. 6

Common Pitfall to Avoid

Do not assume that "more is better" with progesterone dosing. The evidence clearly establishes 400 mg daily as effective, and escalating beyond this dose:

• Lacks supporting evidence for improved outcomes 1
• May expose you and a developing pregnancy to unnecessary medication 4
• Does not address the actual concern about endometrial thickness, which is an estrogen-dependent issue in the follicular phase 3