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Assisted Reproduction and Infertility
The Luteal Phase and Ovarian Stimulation
Human M Fatemi
Medical Director, Centre for Reproductive Medicine, University Hospital, Brussels
Abstract
The luteal phases of all stimulated in vitro fertilisation (IVF) cycles are abnormal. The aetiology of luteal-phase defect (LPD) in stimulated
IVF cycles has been debated for more than three decades. The main cause of the LPD observed in stimulated IVF cycles is related to the
multifollicular development achieved during ovarian stimulation, which completely alters the hormonal environment. It can be postulated
that the main cause of the LPD in stimulated IVF cycles is the supra-physiological levels of steroids secreted by a high number of corpora
lutea during the early luteal phase, which directly inhibits luteinising hormone (LH) release via negative feedback actions at the
hypothalamic–pituary axis level. Luteal-phase support with human chorionic gonadotrophin (hCG) or progesterone after assisted
reproduction corrects the LPD. hCG is associated with a greater risk of ovarian hyperstimulation syndrome (OHSS). Natural micronised
progesterone is not efficient if taken orally. Vaginal and intramuscular progesterone seem to have comparable implantation and clinical
pregnancy rates and delivery rates. However, due to severe side effects, intramuscular progesterone administration should be avoided.
Keywords
Luteal-phase support, ovarian stimulation, luteal-phase defect
Disclosure: The author has no conflicts of interest to declare.
Received: 19 January 2009 Accepted: 16 February 2009
Correspondence: Human M Fatemi, VUB/CRG, Laarbeeklaan 101, 1090 Brussels, Belgium. E:
hmousavi@uzbrussel.be
Luteal Phase secretory transformation of the endometrium due to the progesterone
The luteal phase is defined as the period between ovulation and produced by the corpus luteum. During the secretory phase, a short
either the establishment of a pregnancy or the onset of menses specific period of uterine receptivity towards embryonic implantation
two weeks later.
1
In women and other primates, steroid hormone is designated as the implantation window.
8
The peak of the secretory
production by corpora lutea depends on the presence of continued endometrial activity is around the fourth to seventh post-ovulatory
luteinising hormone (LH) production.
2
If conception and implantation day, coinciding with the time of embryo implantation. A deficient luteal
occur, the developing blastocyst secretes human chorionic phase will have a direct impact on the endometrium and,
gonadotrophin (hCG). The role of hCG produced by the embryo is to consequently, on the implantation and survival of the embryo.
maintain the corpus luteum and its secretions.
3
The estimated onset
of placental steroidogenesis (the luteoplacental shift) occurs during Luteal-phase Defect
the fifth gestational week (as calculated by the patient’s last menses).
4
As early as 1949, the premature onset of menses was recognised as
being indicative of a luteal-phase deficiency of progesterone
The Endometrium production that was shown to be correctable by exogenous
The endometrium is the mucosal lining of the uterine cavity. It is one progesterone administration.
9
The prevalence of a luteal-phase defect
of the main targets of the steroids produced by the corpus luteum. Its (LPD) in natural cycles in normo-ovulatory patients with primary or
basic function is the creation of a suitable environment for embryo secondary infertility was demonstrated to be about 8.1%.
10
nidation. Although implantation could occur in any human tissue, the
endometrium is the only tissue that is not receptive to embryo Pathophysiological alterations of the complex reproductive process
implantation except for during a restricted frame of time called that lead to delayed endometrial maturation characteristic of an LPD
the ‘implantation window’.
5
include disordered folliculogenesis, defective corpus luteum function
and abnormal luteal rescue by the early pregnancy. A variety of
As the major target of sex steroid hormones, the endometrium will clinical conditions such as hyperprolactinaemia, hyperandrogenic
undergo characteristic cycles of proliferation, secretory changes and states, weight loss, stress and athletic training may not result in
tissue shedding in response to ovarian steroid hormones.
6
The oligo- or anovulation, but rather may manifest as a LPD.
11
endometrium proliferates due to the stimulation of oestradiol (E
2
)
produced by the granulose cells in the follicular phase. First, there is The three main causes of an LPD in unstimulated cycles include poor
an increase in mitotic activity, and second, there is the formation of a follicle production, premature demise of the corpus luteum and failure
loose capillary network in the spiral vessels. After ovulation, there is a of the uterine lining to respond to normal levels of progesterone.
26 © TOUCH BRIEFINGS 2009
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