Leukemia inhibitory factor induces cumulus expansion in immature human and mouse oocytes and improves mouse two-cell rate and delivery rates when it is present during mouse in vitro oocyte maturation.
OBJECTIVE
To examine the role of leukemia inhibitory factor (LIF) during in vitro maturation (IVM) on human and mice cumulus expansion and mice oocyte competence by in vitro fertilization (IVF), culture, and embryo transfer (ET).


METHODS
Prospective animal and human study.


METHODS
Serono laboratories and IVF clinic.


METHODS
Healthy women volunteers and 8-week-old female mice.


METHODS
Cumulus compacted human and mice oocytes were matured in IVM media with and without recombinant follicle-stimulating hormone (FSH) and with and without LIF. Mice IVM oocytes with and without 0.2 IU/mL of recombinant FSH; or with and without recombinant FSH + LIF (0.1, 1.0, 1000.0 ng/mL) and ovulated oocytes were in vitro fertilized and cultured. We transferred 395 blastocysts to the uterine horn of 2.5-day pseudopregnant female mice.


METHODS
Cumulus expansion in human and mice oocytes, and two-cell rate, blastocyst rate, and delivered rate of live pups in mice.


RESULTS
In human and mouse oocytes, LIF induced cumulus expansion. When 1000 ng/mL of LIF was added in combination with recombinant FSH, a statistically significant increase in cleavage rate, embryo development rate, and birth rate was observed when compared with oocytes matured with FSH alone.


CONCLUSIONS
Leukemia inhibitory factor induced cumulus expansion similarly in human and mouse cumulus-oocyte complexes, and recombinant FSH plus LIF supplementation during mouse IVM significantly improved oocyte competence as measured by cleavage rate, blastocyst development, and birth rate.
De Matos
Daniel G
DG
EMD Serono Research Institute, Rockland, Massachusetts 02370, USA. dematosdg@yahoo.com
Miller
Kathleen
K
Scott
Richard
R
Tran
Cam Anh
CA
Kagan
David
D
Nataraja
Selva G
SG
Clark
Ann
A
Palmer
Stephen
S
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002970:Cleavage Stage, Ovum / Q000187:drug effects*; D054885:Cumulus Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D005307:Fertilization in Vitro; D043373:Follicle Stimulating Hormone, Human / Q000494:pharmacology; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology*; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology
D005300:Fertility Agents, Female; D043373:Follicle Stimulating Hormone, Human; D053605:Leukemia Inhibitory Factor; D011994:Recombinant Proteins