Morning Mental Wake Up Exercise: Remove a word to make a sentence. Drive slowly curious the car. Daily take planes babies off. Ball the throw high novel.

Morning Mental Wake Up Exercise: Remove a word to make a sentence.

Drive slowly curious the car.

Daily take planes babies off.

Ball the throw high novel.

Shoes give dynamic back the.

He observes occasionally people acceptance.

Delicious hopeful food oranges are.

Sky trustworthy is seamless gray.

Should now withdraw special we.

Us curious sing together let.

Bountiful makes exciting raisins sunlight.

Energy road cat a walks the

Hammer my success the thumb hit.

Ideas willing for intently listen

INFERTILITY

INFERTILITY WORKUP

Checking of OvulationSemen ParameterTubal StatusUterine Cavity Normalcy

INFERTILITY

Normalize hormonal imbalancesDiagnostic laproscopyLuteal phase ultrasoundSonohysterographySlow push HSG

INFERTILITY

Current conventional treatment approach for infertile patient without severe male factor or blocked tubes.

Super-ovulationOperateSuper-ovulationIVF / ICSI

UNEXPLAINED INFERTILITY

Cochran Database articles 2002 & 2005Treatment of sub-fertility with IVF shows no conclusive

benefits

“Overall prognosis with current treatment of infertility” by Collins et al.

Human Reproduction Update, Vol. 10, No.4 pp. 309-316, 2004

“Typical management of infertility would fall short of 50% live births even with extensive utilization of ART. Underlying unknown untreatable factors remain barriers to greater overall success in the treatment of infertility.”

Life table analysis of outcomes In 2004, 126 patient came in for evaluation and 36 did not

remain, leaving 90 patients. 12 of 90 were lost to followup without treatment 10 of 14 did IVF and delivered. This is 71% 39 of 64 who remained for non-ART treatment went on

to deliver. This is 61% 49/78 total patients is 62.8% went on to deliver

Collins et al: Out of 10,000 patients worked up for infertility, 4900 did not stay for treatment, but 30% were pregnant within 2 years.

Of the 5100 who remained for treatment, 42% achieved ongoing pregnancy without using IVF.

Even with extensive IVF usage, pregnancies did not exceed 50% of the treatment group.

Live birth rates estimated in 20 studies involving follow-up of 14,460 infertile couples,1950-2003. Do not include IVF or ICSI treatment.

Overall prognosis with current treatment of infertility, John A Collins et al.

INFERTILITY

Per Cycle Fecundity Rate

As low as 0.5% chance/cycle conceiving spontaneously if unexplained.

With Clomid alone – Increases to 4% / cycleClomid + IUI – 7% / cycleHMG & IUI – 17% / cycleCumulative Pregnancy Rate, short of IVF – 42% / cycle

AT IVF PHOENIXOngoing cumulative pregnancy rate 61% without

using IVF

I began looking for other things to explain the infertility, other than

simply getting gametes together.

Infertility patients have 3-5X more Adverse Pregnancy Outcomes than

the general population.

Unexplained RSA patientsIn the early 1990s we were using low dose heparin and noticed

Increased delivery rates.Less migrainesLess hyperemesisWarmer hands and less livido

UNEXPLAINED INFERTILITY

Arginine

i NOS

Arginase

Nitric Oxide (NO)

Polyamine

Heparin vasodilated via NO

INFERTILITY Elevated Day 3 FSH Levels - >11 Abnormal Clomiphene Citrate Challenge Test

(CCCT) Negative Predictive value

Elevated Day 3 FSH level, not just alive or dead ovaries. Dynamic Ovaries Deaf Ovaries--------due to Hormone Transmission Defect. (FSH or IGF-

1) Depleted Ovaries----due to lack of visible basal antral follicles Dead Ovaries----due to lack of any primordial follicles.

Simple Vasodilation Hormone Transmission Defects Normalized Improved Ovarian response Improved Pregnancy Rates

INFERTILITYViral Insult

Herpes virus familyChronic low grade viral infectionImmune suppressionEnhance TH1 activationAfter doing viral protocol, 50% of infertile

couples (excluding severe male factor and tubal blockage) conceive within 4 cycles, without IVF

25% of infertile and RSA patients.

IGF-1 is permissive to follicle maturation

IGF-1 reverses eNOS uncoupling in DM and Insulin resistance.

INFERTILITY

T Helper Cell 2 (TH2) overexpression

23 Patients failed after all approachesTNF alpha <1.0 in 100% of these extreme

failures

TNF alpha normalized in all, and – 6/13 patients who retried superovulation were able to conceive.

Mostly secondary infertility

Biological Response ModifiersIVIG: may work to remove virally infected WBC WBC immunizations or Killed Steptococcal preps:

believed to reset TH1/TH2 responses. These were introduced for early clinical miscarrying patients, but I have found that this is most helpful in Early Implantation Failure patients. (currently not available in USA)

Recalcitrant thin endometrium---70% improve Chemical losses—moves to clinical pregnancy in 70% Unexplained infertility-no signs of pregnancy but patient

feels something around 7-11 days after ovulation.

So How Do I Make Sense of all of this.

Infertility/RSA patients have 3-5x risk of APO over general population.

Treating for clotting imbalances and viruses and immune dysfunction improves infertility outcomes by 50%, without using IVF.

Inflammation can be due to all of these sources.These sources are affecting nitric oxide balance.Nitric oxide balance may regulate inflammation.Inflammation may causing infertility and APO.

Inflammation effect on NO.Defects in metabolism of Essential Fatty Acids,

BH4, eNOS/Arginase expression or activity Less Nitric Oxide produced per unit time.

Hereditary defects in clotting balance, or acquired defects lead to I/R injury and ROS.

More Nitric Oxide consumed/destroyed per unit time and less delivered.

Viral insults creates endothelial cell vasculitis, and virus affects anti/pro inflammatory prostanoid balance.

Prostanoid balance and metabolism is regulated through Nitric Oxide.

Therapeutic interventions into Inflammatory processes.

Improved NO formation via replacement of BH4, heparin/lovenox stimulation on NOS.

Add L-arginine substrate Limit S-nitrosylation of cysteine from Increasing

Arginase Km Detox homocysteine with folate, prevent cysteine

Limit ROS and Fe lowering of Arginase Km

Decrease NO removal via lowering ROS Antioxidants/exercise/diet-good EFA metabolism Low dose allopurinol to block Xanthine Oxidase

Less uric acid means less WBC ROS formation Less XO means less OH- and O2-.

Less ROS, means less NO quenching Less ROS, means less BH4 destruction. Less ROS, means higher Arginase Km

Therapeutic interventions into Inflammatory processes.

Improved NO formation via replacement of BH4, heparin/lovenox stimulation on NOS.

Add L-arginine substrate Limit S-nitrosylation of cysteine to limit decrease

Arginase Km Limit ROS and Fe lowering of Arginase Km

Decrease NO removal via lowering ROS Antioxidants/exercise/diet Low dose allopurinol to block Xanthine Oxidase

Less uric acid means less WBC ROS formation Less ROS, means less NO quenching Less ROS, means less BH4 destruction. Less ROS, means higher Arginase Km