Mitochondrial DNA depletion in oocytes of HIV-infected antiretroviral-treated infertile women.
BACKGROUND
HIV-infected women under highly active antiretroviral therapy (HAART) undergoing in vitro fertilization (IVF) have a lower pregnancy rate than noninfected controls, which depends on oocyte-related factors. We hypothesized that mitochondrial toxicity caused by antiretrovirals could be the underlying mechanism of such disturbance.


METHODS
We have studied 16 and 19 frozen-thawed oocytes obtained after oocyte retrieval IVF cycles from 8 and 14 infertile HIV-infected and uninfected women, respectively, matched by age. At inclusion, HIV-positive women had been infected for >13 years and had received HAART for >9 years, including at least one nucleoside reverse transcriptase inhibitor. All of them had undetectable HIV viral load and a good immunological status. Mitochondrial DNA (mtDNA) content was determined by quantitative real-time PCR in each individual oocyte.


RESULTS
HIV-infected infertile women on HAART showed significant oocyte mtDNA depletion when compared with uninfected controls (32% mtDNA decrease, P<0.05). This oocyte mtDNA depletion was even greater on those HIV-infected women who failed to become pregnant when compared with controls (39% mtDNA decrease, P=0.03). No significant correlation was found between mtDNA oocyte content and cumulative doses of antiretrovirals or the immunological status of HIV patients.


CONCLUSIONS
Oocytes from infertile HIV-infected HAART-treated women show decreased mtDNA content, and this could explain their poor reproductive outcome.
López
Sònia
S
Mitochondrial Research Laboratory, Internal Medicine Department, IDIBAPS, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
Coll
Oriol
O
Durban
Mercè
M
Hernàndez
Sandra
S
Vidal
Ricard
R
Suy
Anna
A
Morén
Constanza
C
Casademont
Jordi
J
Cardellach
Francesc
F
Mataró
Daniel
D
Miró
Oscar
O
Garrabou
Glòria
G
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005307:Fertilization in Vitro; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007246:Infertility / Q000150:complications / Q000628:therapy; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects*
D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial