Table 5.
Clinical studies investigating the role of NO in IVF.
| Authors | Type of Study | Population Considered | Effects |
|---|---|---|---|
| Battaglia et al., 2003 [55] | Observational (pilot) study | -23 women undergoing an IVF-ET program | -Embryonic secretion of NO demonstrated by higher mean nitrite/nitrate concentrations present in the culture medium of each embryo -The mean nitrite/nitrate concentrations in the embryo culture medium were significantly higher in patients that became pregnant. |
| Lipari et al., 2009 [56] | Observational study | -11 women undergoing an IVF-ET program | -Nitric oxide metabolite levels in the insemination media were higher in embryos that progressed to blastocysts by culture day 5 compared with those that did not. |
| Gallinelli et al., 2008 [57] | Study population | -179 women undergoing an IVF-ET program: -123 women with fresh oocytes. -56 oocyte thawing cycles |
-Higher NO production in embryos derived from ICSI than from IVF after 52 h of culture. -Embryos derived from fresh oocytes produced more NO than embryos from thawed oocytes after 48 and 52 h of culture. |
| Ohl et al., 2002 [58] | Prospective, double-blind, randomized, placebo-controlled trial | -138 patients undergoing an IVF-ET program: -70 patients treated with nitroglycerin-68 with placebo |
-No improved implantation or pregnancy rates after NTG treatment on the day before embryo transfer. |
| Lee et al., 2000 [59] | Observational study | -43 patients undergoing an IVF-ET program | -No significant correlation between the concentrations of NO and TNF-alpha in follicular fluid. -NO levels in follicular fluid were altered in infertility-associated diseases. -TNF-alpha levels but not NO levels influenced oocyte quality. |
| Lee et al., 2004 [60] | Prospective, case-control study | -36 patients undergoing an IVF-ET program: -18 patients undergoing an IVF-ET program with tubal or peritoneal factor -18 female partners from couples with male factor infertility |
-Higher follicular NO levels associated with advanced fragmentation of embryos. -Higher serum NO levels found among non-pregnant patients with tubal or peritoneal factor infertility. |
| Vignini et al., 2008 [61] | Observational study | -15 patients undergoing an IVF-ET program | -Mean concentration of the NO follicular fluid was significantly higher in patients with embryos showing significant or severe fragmentation or blastomeres of distinctively unequal size than those with good-quality embryos. -Direct correlation between follicular NO and embryo grading and an inverse correlation between follicular NO and serum 17beta-estradiol. |
| Bergandi et al., 2014 [62] | Observational study | -40 women undergoing an IVF-ET program | -iNOS and HO-1 mRNAs and proteins significantly higher in cumulus cells (CCs) corresponding to oocytes that were not fertilized in comparison to CCs whose corresponding oocytes showed normal fertilization. |
CCs—Cumulus cells; ET—embryo transfer; HO-1—Heme oxygenase 1; ICSI—intracitoplasmic sperm injection; iNOS—inducible nitric oxide synthase; IVF—In-vitro fertilization; NO—Nitric oxide; NTG—Nitroglycerin; TNF-alpha—Tumor necrosis factor alpha.