PRACTITIONERS OF EMBRYO TRANSFER (ET) IN CATTLE AND CLINICIANS DURING ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) IN WOMEN USE SIMILAR HORMONAL TREATMENTS TO STIMULATE OVARIES (SUPEROVULATION) TO PRODUCE MULTIPLE HIGH QUALITY EGGS CAPABLE OF BEING FERTILIZED AND PRODUCING LIVE OFFSPRING. IN CATTLE, ET IS USED TO ENHANCE NUMBER OF OFFSPRING BORN FROM HIGH GENETIC MERIT COWS WHILE ART IS USED BY CLINICIANS TO IMPROVE ABILITY OF COUPLES WITH POOR FERTILITY TO HAVE CHILDREN. DESPITE ADVANCES IN ET/ART OVER THE PAST 20 YEARS, SUPEROVULATION RESULTS IN HIGH EGG AND EMBRYO WASTAGE, UNPREDICTABLE OUTCOMES (ZERO TO AN UNKNOWN NUMBER OF LIVE BIRTHS), AND HIGH COSTS THAT HINDER WIDESPREAD USE OF ET IN THE CATTLE INDUSTRY AND USE OF ART BY CHILDLESS COUPLES. ONE OF THE MAJOR CAUSES OF THE UNPREDICTABLE NATURE OF ET/ART MAY BE DIRECTLY RELATED TO THE GAP IN OUR UNDERSTANDING OF THE BEST DOSE OF HORMONE TO USE DURING SUPEROVULATION TO OPTIMIZE NUMBER OF HIGH QUALITY EGGS CAPABLE OF BEING FERTILIZED AND DEVELOPING INTO LIVE OFFSPRING. FOR EXAMPLE, TREATMENT OF CATTLE OR WOMEN WITH RELATIVELY MODERATE TO HIGH DOSES OF THE HORMONE, FOLLICLE STIMULATING HORMONE (FSH), WHICH IS ROUTINELY USED TO STIMULATE OVARIES DURING ET/ART, DECREASES NUMBER OF OVULATIONS, NUMBER OF HIGH QUALITY EGGS AND EMBRYOS RECOVERED, AND LIVE BIRTH RATES COMPARED WITH LOWER FSH DOSES. IN ADDITION, APPROXIMATELY 15% TO 25% OF CATTLE AND WOMEN, WHICH HAVE A RELATIVELY SMALL NUMBER OF HIGH QUALITY EGGS AND FOLLICLES IN OVARIES (SMALL OVARIAN RESERVE), ALSO RESPOND POORLY TO ET/ART COMPARED WITH INDIVIDUALS WITH A LARGER OVARIAN RESERVE. THUS, ANOTHER GAP IN OUR UNDERSTANDING OF THE CAUSE OF THE UNPREDICTABLE OUTCOMES OF ET/ART IS WHETHER FSH DOSES CAN BE OPTIMIZED TO IMPROVE RESPONSE (LIVE BIRTH RATES) OF INDIVIDUALS WITH A SMALL OVARIAN RESERVE TO SUPEROVULATION. OUR STUDIES IN CATTLE SHOW MAXIMAL RESPONSE TO SUPEROVULATION (SOVMAX), DEFINED AS THE FSH DOSE YIELDING THE GREATEST NUMBER OF OVULATORY FOLLICLES, REACHES A PLATEAU. FSH DOSES GREATER THAN SOVMAX DECREASE OVULATORY FOLLICLE NUMBER AND NUMBER OF TRANSFERABLE EMBRYOS, AND INCREASES NUMBER OF DEGENERATE EMBRYOS. MOREOVER, MODERATE TO HIGH FSH DOSES USED DURING ART DECREASE LIVE BIRTH RATES IN WOMEN, AND MOST WOMEN ARE TREATED WITH EXCESSIVE FSH DOSES THAT DO NOT OPTIMIZE LIVE BIRTH RATES. THESE STUDIES SUPPORT OUR CENTRAL HYPOTHESIS THAT FSH DOSES LESS THAN OR EQUAL TO SOVMAX ARE OPTIMAL WHILST FSH DOSES GREATER THAN SOVMAX DECREASE OVULATORY FOLLICLE NUMBER/FUNCTION, OOCYTE AND EMBRYO QUALITY, AND EMBRYO SURVIVAL. BECAUSE A SMALL OVARIAN RESERVE IS A MAJOR CONTRIBUTOR TO INFERTILITY NOT ONLY IN CATTLE BUT ALSO WOMEN, THE LONG-TERM GOAL OF THIS PROJECT IS TO IMPROVE ET/ART IN CATTLE/WOMEN BY BETTER UNDERSTANDING HOW LOW ANTRAL FOLLICLE COUNT (AFC; INDICATOR OF SMALL OVARIAN RESERVE) IN INDIVIDUALS (DONORS) IMPACTS CAPACITY OF FSH, WHICH IS USED DURING SUPEROVULATION TO STIMULATE OVARIES, TO ENHANCE OVULATORY FOLLICLE NUMBER AND FUNCTION, EGG AND EMBRYO QUALITY, AND EMBRYO SURVIVAL, AND TO DETERMINE THE ASSOCIATED MECHANISMS. SPECIFIC AIMS ARE: 1) TO ESTABLISH THE RELATIONSHIP BETWEEN FSH DOSE AND SOVMAX, 2) TO DETERMINE IF FSH DOSES GREATER THAN SOVMAX REDUCE EGG QUALITY AND OVULATORY FOLLICLE FUNCTION RESULTING IN HIGH EGG AND EMBRYO WASTAGE AND REDUCED EMBRYO SURVIVAL, AND 3) TO TEST POTENTIAL THERAPIES TO INCREASE RESPONSE TO SUPEROVULATION IN INDIVIDUALS WITH A SMALL OVARIAN RESERVE. RESULTS WILL ESTABLISH FOR THE FIRST TIME IF SOVMAX AND CORRELATED MARKERS THAT CAN BE MEASURED IN BLOOD CAN BE USED TO OPTIMIZE FSH DOSAGES TO IMPROVE ET/ART SUCCESS, IF FSH DOSES EXCESSIVE TO THE SOVMAX IMPAIR OVULATORY FOLLICLE FUNCTION AND DIMINISHES EGG AND EMBRYO QUALITY AND EMBRYO SURVIVAL, AND IF REDUCTION IN NATURAL SECRETION OF FSH BY THE COW AND AFC IMPROVES OVULATORY FOLLICLE NUMBER AND EMBRYO YIELD/QUALITY AFTER IVF FOR INDIVIDUALS WITH A SMALL OVARIAN RESERVE AND NATURALLY HIGH FSH SECRETION. UPON COMPLETION OF PROPOSED STUDIES, A BETTER UNDERSTANDING OF THE IMPACT OF FSH DOSES ON OVULATORY FOLLICLE FUNCTION DURING ET/ART WILL BE ESTABLISHED PROVIDING THE BASIS FOR DEVELOPMENT OF POTENTIAL NEW PROTOCOLS TO IMPROVE RESPONSE OF INDIVIDUALS WITH A LOW AFC AND SMALL OVARIAN RESERVE TO OVARIAN STIMULATION, WHICH MAY HAVE TRANSLATIONAL RELEVANCE TO REDUCE EGG AND EMBRYO WASTAGE AND IMPROVE SUCCESS OF ET AND ART OUTCOMES IN CATTLE AND HUMANS.