Progesterone — Role in Fertility, IVF & Luteal Phase Support

Progesterone has two critical roles in fertility: (1) In natural cycles: after ovulation, the corpus luteum (ruptured follicle) produces progesterone to transform the endometrium from its proliferative state to a secretory state — creating the "implantation window" where an embryo can implant and grow. A mid-luteal serum progesterone >10 ng/mL confirms adequate ovulation and corpus luteum function. (2) In IVF: stimulation protocols suppress the pituitary, which impairs corpus luteum function. Vaginal progesterone pessaries (Cyclogest 400mg) or oral micronised progesterone (Utrogestan) are prescribed from the day of egg retrieval to replace this natural production until the placenta takes over at 10–12 weeks.

In a natural cycle, serum progesterone measured 7 days after ovulation (Day 21 in a 28-day cycle, or "Day LH+7" if cycle length varies) should be: >3 ng/mL = ovulation has occurred; >10 ng/mL = adequate corpus luteum function; 10–30 ng/mL = normal mid-luteal range; <3 ng/mL = anovulation (no ovulation this cycle). In IVF medicated FET cycles, progesterone should ideally be >10–15 ng/mL on the day of embryo transfer. Some studies suggest >20 ng/mL for optimal outcomes — monitoring serum progesterone in FET cycles is increasingly standard practice.

The most common route is vaginal pessaries: Cyclogest 400mg inserted vaginally twice daily (BD) — provides local endometrial effect with minimal systemic absorption; or Crinone 8% gel once daily. Oral micronised progesterone (Utrogestan 200mg) can be inserted vaginally for similar local effect. For some FET protocols, especially when higher serum levels are needed, intramuscular (IM) progesterone in oil (50mg daily) is used — it gives the highest blood levels but causes injection site soreness. Subcutaneous aqueous progesterone (Prolutex) is a newer option with less discomfort. Route choice depends on the clinic protocol and individual response.

Low progesterone in early pregnancy is strongly associated with miscarriage, though whether it is a cause or consequence is debated — a failing pregnancy produces less progesterone, not the other way around in most cases. However, the PRISM trial (2019, NEJM) showed that vaginal progesterone (400mg BD) given to women with bleeding in early pregnancy and a history of previous miscarriage significantly increased live birth rates. Current NICE guidance recommends progesterone supplementation for women with threatened miscarriage and at least one previous miscarriage. In IVF, there is clear evidence that adequate luteal phase support with progesterone is mandatory for successful implantation.

In most IVF protocols, progesterone supplementation is continued until 10–12 weeks of pregnancy, when the placenta has taken over progesterone production (the "luteo-placental shift"). Stopping progesterone before this transition can cause progesterone withdrawal and increase miscarriage risk. The exact timing varies by clinic and individual response. Progesterone should NEVER be stopped abruptly in early IVF pregnancy without specialist advice. If a pregnancy scan confirms a missed miscarriage or non-viable pregnancy, progesterone can be stopped — it does not prevent the miscarriage from occurring or "keep a non-viable pregnancy going".