282Artificial Insemination in Farm Animalsis withheld until the lead follicle reaches 14 mm or more. Moreover, evidence indicates thatincreased LH exposure during early follicular development may be detrimental andpredispose to lower pregnancy rates (Kolibianakis E, et al., 2002; Kolibianakis EM, et al.,2003; Kolibianakis EM, et al., 2003; Kolibianakis E, et al., 2003). In theory, pre-treatment withan OC might prove quite useful by suppressing LH and androgen levels before stimulationbegins, decreasing exposure during early follicular development and the risk of rising LHlevels before antagonist treatment starts. Preliminary OC suppression and later antagonisttreatment may help to limit the follicular response to gonadotropin stimulation whilepreserving the option to use an agonist to trigger final oocyte maturation. Theseconsiderations simply serve to illustrate that GnRH antagonists are not a panacea and arenot necessarily the best choice even for women with PCOS. Antagonist stimulationprotocols are advocated for poor responders, primarily because they avoid the suppressiveeffects that agonists can have on follicular response and can prevent the premature LHsurges observed commonly in women stimulated with gonadotropins alone (Surrey ES &Schoolcraft WB., 2000). However, evidence is insufficient to indicate they yield resultsconsistently better than other stimulation regimens (Pandian Z, et al., 2010; Centers forDisease Control and Prevention, Atlanta, GA, 2009).10. Ovarian reserveThe concept of ovarian reserve, generally defined as the size and quality of the remainingovarian follicular pool, and the various methods for its measurement. The total number ofoocytes in any given women is genetically determined and inexorably declines throughoutlife, from approximately 1–2 million at birth, to about 300,000 at puberty, 25,000 at age 40,and fewer than 1,000 at menopause (Battaglia DE, et al., 1996; Faddy MJ & Gosden RG,1996). The rate of follicular depletion is not constant, but increases gradually as the numberof follicles remaining decreases (Nilsson E, et al., 2007; Adhikari D & Liu K, 2009; Da Silva-Buttkus P, et al., 2009; Coxworth JE, & Hawkes K, 2010). As the size of the remainingfollicular pool decreases, circulating inhibin-B levels (derived primarily from smaller antralfollicles) decrease, resulting in lower levels of feedback inhibition and a progressive increasein serum follicle-stimulating hormone (FSH) levels, most noticeably during the earlyfollicular phase (Klein NA, et al., 1996; Welt CK, McNicholl DJ, Taylor AE, et al; Hale GE, etal., 2007 ; Knauff EA, et al., 2009; Burger HG, et al., 2008). Increasing inter-cycle FSHconcentrations stimulate earlier follicular recruitment, resulting in advanced folliculardevelopment early in the cycle, an earlier rise in serum estradiol levels, a shorter follicularphase, and decreasing overall cycle length (Klein NA, et al., 2002; de Koning CH, et al.,2008).The physiology of reproductive aging provides the foundation for all contemporary tests ofovarian reserve. In clinical practice, the basal early follicular phase (cycle day 2–4) FSH levelis the most common test, but antimüllerian hormone (AMH) and antral follicle count arealternatives having significant potential advantages. As basal FSH levels increase, peakestradiol levels during stimulation, the number of oocytes retrieved, and the probability forpregnancy or live birth decline steadily (Pearlstone AC, et al., 1992; Scott Jr RT & HofmannGE, 1995; Bukman A, & Heineman MJ, 2001). With current assays (using IRP 78/549), FSHlevels greater than 10 IU/L (10–20 IU/L) have high specificity (80–100%) for predicting poorresponse to stimulation, but their sensitivity for identifying such women is generally low(10–30%) and decreases with the threshold value (Broekmans FJ, et al., 2006) . Although
Reproductive Endocrinology Diseases: Hormone Replacement and Therapy for Peri/Menopause 283most women who are tested have a normal result, including those with a diminishedovarian reserve (DOR), the test is still useful because those with abnormal results are verylikely to have DOR. In a 2008 study, an FSH concentration above 18 IU/L had 100%specificity for failure to achieve a live birth (Scott Jr RT, et al., 2008). The basal serumestradiol concentration, by itself, has little value as an ovarian reserve test (Hazout A, et al.,2004; Eldar-Geva T, et al., 2005; McIlveen M, et al., 2007), but can provide additionalinformation that helps in the interpretation of the basal FSH level. An early elevation inserum estradiol reflects advanced follicular development and early selection of a dominantfollicle (as classically observed in women with advanced reproductive aging), and willsuppress FSH concentrations, thereby possibly masking an otherwise obviously high FSHlevel indicating DOR. When the basal FSH is normal and the estradiol concentration iselevated (>60–80 pg/mL), the likelihood of poor response to stimulation is increased andthe chance for pregnancy is decreased (Evers JL, et al., 1998; Buyalos RP, al., 1997). Whenboth FSH and estradiol are elevated, ovarian response to stimulation is likely to be verypoor. Antimüllerian hormone (AMH) derives from pre-antral and small antral follicles.Levels are gonadotropin-independent and vary little within and between cycles (Fanchin R,et al., 2005; Tsepelidis S, et al., 2007; Hehenkamp WJ, et al., 2006). The number of smallantral follicles correlates with the size of the residual follicular pool and AMH levels declineprogressively with age, becoming undetectable near the menopause (Sowers MR, et al.,2008; van Rooij IA, et al., 2004; van Rooij IA, et al., 2005).10.1 Oocyte and ovarian tissue cryopreservationEach year, cancer occurs in approximately 100 per 100,000 women under age 50 in theUnited States. Chemotherapy and radiation therapy for malignant and non-malignantsystemic disease very often results in ovarian failure. Women with cancer and other seriousillnesses requiring treatments that pose a serious threat to their future fertility haverelatively few options. In some cases, the ovaries may be moved out of the radiation field.Treatment with GnRH agonists has been suggested as a way to protect the gonads from theinsult of chemotherapy, but there is no convincing evidence for its efficacy. Althoughembryo banking is effective, the time required for stimulation and retrieval are oftenprohibitive. With recent advances in cryobiology, oocyte and ovarian tissuecryopreservation hold promise as methods to preserve reproductive potential (Shaw JM, etal., 2000).10.2 Oocyte cryopreservationAlthough the first pregnancy resulting from oocyte cryopreservation was reported in 1986,(Chen C, 1986), success rates achieved with the technology were historically very low, andonly recently improving. The primary obstacle was the poor survival of oocytes, which arefragile due to their size, high water content, and chromosomal arrangement; the meioticspindle is easily damaged by intracellular ice formation during freezing or thawing (ShawJM, et al., 2000). Germinal vesicle stage oocytes are hardier, (Boiso I, et al., 2002), butprogress with in vitro maturation of immature oocytes has been slow. Another obstacle washardening of the zona pellucida, which interfered with normal fertilization. The improvedsurvival of cryopreserved oocytes today relates primarily to modifications in the sucroseand sodium concentrations in traditional “slow-freeze” protocols, (Fabbri R, et al., 2001;Stachecki JJ & Willadsen SM, 2000; Bianchi V, et al., 2007; De Santis L, et al., 2007), changes.,
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