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Assisted Reproduction and Infertility
objective was to compare the endometrial histology on day 21 of Human Chorionic Gonadotropin
the artificial cycle in patients with POF treated with oral DG versus Since it was found that the corpus luteum can be rescued by the
vaginal progesterone as progestins. After sufficient oestrogen administration of hCG, this treatment has become the standard of
endometrial priming, we found that exogenous administered care for luteal support.
By stimulating the corpora lutea, hCG is an
vaginal micronised progesterone was significantly more effective indirect form of luteal support. It is known to generate an increase
than oral dydrogesterone in creating an ‘in-phase’ secretory in E
and progesterone concentrations, thus rescuing the failing
This conclusion corroborates earlier studies.
corpora lutea in stimulated IVF cycles.
The administration of hCG
has also been shown to increase the concentrations of placental
Vaginal Progesterone protein 14, integrin αν and relaxin (lutel peptide hormone), which
The intravaginal route of progesterone supplementation in IVF has been shown to increase at the time of implantation.
has gained wide application as a first-choice luteal-support meta-analysis published by Pritts and Atwood in 2002,
regimen, mainly due to patient comfort and effectiveness.
shown to be equally effective as progesterone for luteal-phase
Following intravaginal administration of progesterone, high uterine support with respect to pregnancy rates. The disadvantage of using
progesterone with low peripheral serum values are observed, due hCG for luteal support stems from its potential for increasing
to counter-current exchange in progesterone transport between hyperstimulation rates compared with other treatments or no
anatomically close blood vessels
and due to the uterine first- treatment at all. Significant increases in hyperstimulation rates
pass effect, where liver metabolisation is absent.
There is have been confirmed in several studies.
With regard to ovarian
increasing evidence in the literature that vaginal progesterone is at hyperstimulation syndrome, one should therefore be cautious with
least as effective as IM progesterone at providing luteal support in the administration of hCG for luteal supplementation in stimulated
Luteal support with hCG should be avoided if E
are above 2,500–2,700pg/ml on the day of hCG administration,
Intramuscular Progesterone and if the number of follicles is above 10.
With IM progesterone, supplementation is given as an injection of
natural progesterone in oil.
In 1985, Leeton et al. first Gonadotropin-releasing Hormone Agonist –
demonstrated the extension of the luteal phase of stimulated IVF A Novel Luteal-phase Support?
cycles treated with IM progesterone 50mg. The doses of IM GnRH agonist was recently suggested as a novel luteal-phase
progesterone used for luteal phase support vary from 25 to 100mg support that may act upon pituitary gonadotrophs, the
per day without any significant difference in outcome.
This route endometrium and the embryo itself.
It has been hypothesised that
of administration is often associated with a number of side effects, GnRH agonists may support the corpus luteum by stimulating the
including painful injections and a rash,
causing a lack of secretion of LH by pituitary gonadotroph cells or by acting directly
enthusiasm for this treatment modality.
Injections of progesterone on the endometrium through the locally expressed GnRH
in oil can also lead to inflammatory reactions and abscedations.
Despite these initial encouraging results, it is too early
addition, several case reports have been published in which to adopt this treatment wholesale. With regard to safety, great
patients receiving IM progesterone for luteal supplementation have concern exists about possible adverse effects on oocytes and,
developed acute eosinophilic pneumonia.
This drug-induced more importantly, on embryos.
To establish a potential positive
disease shows that the use of IM progesterone can also be role of GnRH agonist administration in the luteal phase of
associated with severe morbidity in otherwise healthy young stimulated IVF cycles, further large prospective trials are needed.
The latest meta-analysis published in 2005 confirmed
that there is no significant difference between vaginal and IM The Duration of Luteal-phase Support
progesterone on ongoing pregnancy rates.
It can be concluded There is no indication to support the generally accepted practice of
that the vaginal administration of progesterone is a viable prolonging progesterone supplementation during early pregnancy.
alternative to the painful and possibly dangerous daily Once the hCG is positive, there is no further need for continuing the
intramuscular injections of progesterone used for luteal support in luteal-phase support.
It would appear that the increase in
IVF. On the basis of presented evidence, IM progesterone is not endogenous HCG levels during early pregnancy makes up for any
recommended as a first-choice luteal phase support method in possible lack of endogenous LH that has been caused by stimulated
stimulated IVF cycles. IVF cycles. First-trimester progesterone supplementation in IVF may
support early pregnancy through seven weeks by delaying a
Progesterone plus Oestradiol miscarriage, but it does not improve live birth rates.
The two most important hormones produced by the corpus luteum
are progesterone and E
The role of progesterone as luteal Conclusions
support in stimulated cycles is well established.
However, it has The cause of LPD in stimulated IVF cycles seems to be related to
not yet been clearly demonstrated whether additional the supra-physiological levels of steroids. Luteal-phase support
supplementation of E
in stimulated IVF cycles is beneficial.
with HCG or progesterone after assisted reproduction results in an
Studies were conducted to examine whether the probability of increased pregnancy rate.
HCG is associated with a greater risk of
pregnancy is increased by adding oestrogen to progesterone for ovarian hyperstimulation syndrome (OHSS). Luteal support with
luteal-phase support in patients receiving IVF treatment. However, hCG should be avoided if E
and if the number of
the meta-analysis by Kolibianakis et al.
suggests that the addition follicles is >10.
Natural micronised progesterone is not efficient if
of oestrogen to progesterone for luteal-phase support does not taken orally.
Vaginal and IM progesterone seem to have similar
increase the probability of pregnancy in IVF in GnRH agonist or implantation and clinical pregnancy rates and delivery rates.
antagonist cycles. addition of E
to progestin for luteal-phase support seems not to be
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