Is the Corpus Luteum Missing in IVF?
No, the corpus luteum is not missing in IVF, but it is dysfunctional and produces inadequate progesterone due to the supraphysiological ovarian stimulation, requiring exogenous progesterone supplementation (luteal phase support) to optimize pregnancy rates. 1, 2
Why the Corpus Luteum is Dysfunctional in IVF
Supraphysiological stimulation disrupts normal luteal function: The high-dose gonadotropin stimulation used to produce multiple oocytes in IVF (rather than the single oocyte in a natural cycle) results in a dysfunctional luteal phase that is insufficient to support implantation and maintain pregnancy 2
GnRH agonist protocols compound the problem: When GnRH agonists are used in the long protocol (which has been standard for over a decade), the suppression of endogenous gonadotropins further impairs corpus luteum function, making progesterone supplementation essential 3
The corpus luteum exists but underperforms: Multiple corpora lutea form after retrieval of multiple oocytes, but these structures do not produce adequate progesterone levels before the pregnancy test, necessitating exogenous progesterone during this critical window 1
Evidence for Corpus Luteum Presence and Lifespan in IVF
The corpus luteum does form and can be visualized: After successful IVF with singleton pregnancy, the corpus luteum can be identified on transvaginal ultrasound as a <3-cm cystic lesion with a thick wall, with or without internal echoes 4
Functional lifespan is approximately 72 days: In GnRH agonist/hMG-stimulated IVF cycles resulting in singleton pregnancy, the corpus luteum has an average functional lifespan of 72 ± 25 days, as measured by 17α-hydroxyprogesterone levels 5
The corpus luteum remains critical in early IVF pregnancy: Just as in natural conception, the corpus luteum produces progesterone that supports pregnancy for approximately 6-8 weeks until placental steroidogenesis takes over around 8-10 weeks of gestation 4, 1
Clinical Implications for Luteal Phase Support
Progesterone supplementation is mandatory in IVF: Because the corpus luteum does not produce quite enough progesterone before the pregnancy test in IVF cycles where normal hormones are switched off, extra progesterone is needed during this time 1
The "freeze-all" strategy affects luteal support needs: When trophectoderm biopsy at the blastocyst stage is performed for preimplantation genetic testing and a freeze-all embryo strategy is applied, GnRH antagonist protocols are recommended for high responders, which also impacts luteal phase requirements 6
Timing of hCG trigger matters: After ovarian stimulation, hCG (5000-10,000 IU) is administered, and oocyte retrieval is performed within 36-38 hours; the type of trigger used affects the degree of luteal phase support required 6, 2
Important Caveats
The corpus luteum is present but inadequate, not absent: The distinction is critical—the problem is not that the corpus luteum is missing, but that it cannot produce sufficient progesterone due to the altered hormonal milieu created by controlled ovarian hyperstimulation 2, 3
Natural cycle IVF has different luteal dynamics: In minimal stimulation or natural cycle protocols (sometimes used for poor responders), the corpus luteum function may be closer to physiological, though these approaches carry risks of low oocyte retrieval and no transferable embryos 6
Avoid confusion with corpus luteum absence in other contexts: The corpus luteum can truly be absent in anovulatory cycles or after oophorectomy, but this is fundamentally different from the IVF situation where multiple corpora lutea form but function suboptimally 4