Luteal phase support during assisted
reproduction
In vitro fertilization
Progesterone supplementation is used for luteal support after in
vitro fertilization (IVF).2 In this setting,
progesterone is predominantly administered as a vaginal preparation,
although preference differs by geographical
region.2,13 A meta-analysis of RCTs found that neither
the route of administration of progesterone (IM, vaginal, oral) nor
progestogen type (micronised progesterone or synthetic) affected the
outcome of luteal phase support for assisted reproduction techniques
(ART), including IVF and intracytoplasmic sperm injection (ICSI), with
respect to live birth/ongoing pregnancy, clinical pregnancy or
miscarriage rates.14
The results of RCTs evaluating oral NMP after IVF have been mixed
(Table 1 ). Supplementation with oral NMP after IVF
significantly increased luteal phase serum progesterone levels and
prolonged the duration of the luteal phase compared with no
supplementation.15 Two studies comparing oral and
vaginal NMP found similar rates of clinical pregnancy and ongoing
pregnancy with either approach,16,17, although one
study reported a significantly lower implantation rate with oral versus
vaginal NMP.17 Likewise, a prospective randomised
study which compared oral NMP and IM progesterone for luteal support in
patients undergoing IVF found that, while the implantation rate was
lower with oral NMP, the clinical pregnancy rate did not differ
significantly.18 A case-control study reported that a
combination of oral plus vaginal NMP provided a similar rate of ongoing
pregnancy, but a lower abortion rate, to that seen with vaginal NMP
alone.19
Intrauterine insemination
Intrauterine insemination (IUI) is
used in the management of various types of infertility, including mild
male infertility, mild endometriosis, and unexplained
infertility.20 It is a relatively low-cost treatment
and less invasive and psychologically demanding than IVF and ICSI
procedures. IUI can be associated with pregnancy rates of 10–20% per
cycle.21
Use of oral NMP in the IUI setting has been evaluated largely in
observational studies (Table 1 ). A prospective observational
analysis of 591 IUI cycles in which a single follicle was developed
found that the clinical pregnancy rate was improved with oral NMP
compared with no luteal support.22 A large
retrospective analysis of 1779 patients found no significant difference
in pregnancy outcomes (rates of clinical pregnancy, biochemical
pregnancy, early miscarriage, and ectopic pregnancy) between recipients
of oral NMP, dydrogesterone, or vaginal NMP.23
Two small, open-label, observational studies compared success rates in
the first cycle of IUI with progesterone luteal support using NMP-SR or
dydrogesterone in women with unexplained infertility (Table 1 ).
Mean serum progesterone levels were maintained at ≥ 14 ng/mL during the
mid-luteal phase in most patients in both treatment groups in both
studies.12,20 First-cycle biochemically-confirmed
pregnancy rates were 6.7% and 11% per study in patients treated with
NMP-SR and 3.3% and 30% per study in patients treated with
dydrogesterone. Possible reasons proposed by Gopinath and Desai for low
pregnancy rates were monofollicular development in patients undergoing
natural IUI cycles, a trend towards a low motility fraction, and
evaluation of the first cycle only.20