Implantation rates after in vitro fertilization, and treatment of infertility and early pregnancy loss with a nitric oxide donor or substrate alone or in combination with progesterone, and a method for contraception with nitric oxide inhibitors in combination with antiprogestins or other agents
First Claim
1. A method for improvement of implantation rates in a pregnant female mammal after in vitro fertilization which comprises administering to an afflicted female an amount of nitric oxide synthase substrate, a nitric oxide donor, or both, effective to raise the blood level of circulating L-arginine to at least about 50-5000 μ
- molar above the normally 50-1000 μ
molar circulating levels and, optionally, also a progestin or, both of an estrogen and a progestin, in amounts effective to increase the pregnancy rates.
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Accused Products
Abstract
A method is provided for the improvement of implantation rates and/or pregnancy rates in a female mammal, comprising administering to a female mammal in whom pregnancy is desired an effective amount of
(a) a nitric oxide synthase substrate, a nitric oxide donor, or both, optionally in combination with
(b) a progestin, and,
(c) optionally, in further combination with an estrogen. A method is also provided for fertility control for a female mammal, comprising administering to a female mammal in whom pregnancy is not desired and at risk for becoming pregnant an effective amount of nitric oxide synthase inhibitor in combination with an antiprogestin. Pharmaceutical compositions are also provided.
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Citations
47 Claims
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1. A method for improvement of implantation rates in a pregnant female mammal after in vitro fertilization which comprises administering to an afflicted female an amount of nitric oxide synthase substrate, a nitric oxide donor, or both, effective to raise the blood level of circulating L-arginine to at least about 50-5000 μ
- molar above the normally 50-1000 μ
molar circulating levels and, optionally, also a progestin or, both of an estrogen and a progestin, in amounts effective to increase the pregnancy rates. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 16, 17, 18, 19, 20, 21)
- molar above the normally 50-1000 μ
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12. The method of fertility control with a nitric oxide synthase inhibitor in combination with an antiprogestin
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15. A pharmaceutical composition comprising an admixture of (a) a nitric oxide synthesis substrate, (b) a nitric oxide donor or both, and optionally, also at least one of (c) a progestin, (d) and an estrogen in amounts effective to increase the pregnancy rates or ameliorate the symptoms of threatening abortion in a pregnant or infertile female mammal when administered thereto in an amount effective of estrogen equivalent to 1-2 mg of estradiol and an amount of the progestin bioequivalent to 50-300 mg of injected progesterone and an amount of the nitric oxide synthase substrate, nitric oxide donor or both effective to raise the blood level of circulating L-arginine to at least about 50-5000 μ
- molar above the normally 50-1000 pmolar circulating levels or raise the nitric oxide donor levels to about 10 nM to 100 μ
molar.
- molar above the normally 50-1000 pmolar circulating levels or raise the nitric oxide donor levels to about 10 nM to 100 μ
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22. A method of improving implantation rates and/or pregnancy rates in a female mammal, comprising administering to a female mammal in whom pregnancy is desired an effective amount of
(a) a nitric oxide synthase substrate, a nitric oxide donor, or both, optionally in combination with (b) a progestin, and, (c) optionally, in further combination with an estrogen.
- 33. A method of fertility control for a female mammal, comprising administering to a female mammal in whom pregnancy is not desired and at risk for becoming pregnant an effective amount of nitric oxide synthase inhibitor in combination with an antiprogestin.
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39. A pharmaceutical composition comprising an admixture of effective amounts of
(a) a nitric oxide synthesis substrate, a nitric oxide donor or both; - and
(b) a progestin, and optionally, (c) an estrogen, in amounts effective to increase the pregnancy rates or ameliorate the symptoms of impending abortion in pregnant female mammal or a female mammal with impaired fertility, wherein the amount of nitric oxide synthase substrate, nitric oxide donor or both administered is effective to raise the blood level of circulating L-arginine in said female to whom the composition is administered to at least about 50-5000 μ
molar above the normally 50-1000 μ
mole circulating levels and/or is effective to raise the nitric oxide donor level to about 1-1000 nmolar;
the amount of progestin administered is bioequivalent to 50-300 mg of injected progesterone; and
the amount of estrogen administered, if any, is bioequivalent to 1-2 mg of estradiol.
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Specification