Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Ovarian Stimulation ~ Nonhuman Primal; P0ert F. Williams, MAD. IN~JCllON -this article ~~l refries ~ - As of ovarian stimOa~cion In mailman primates. Sing the majority of reproductive biology Awards with roan primates is urxlertal~n with macaques (if. Platte - rhesus arm M. fasia~ar~s - ~rKr~lgus), He fog of this article will be on ~e nonnal and stimulated follir~~loger~ic prong In the gags Mdcaca. R~bly, i~ regulating folli~ogenesis, avulatioa,, Aural fur~ic~n and He Mensa 1~1 ~1 ~ AL an; an; 1 =_ : ~ ~1~ it ~~ ~ . _~ ~ ~~ __ ~ ~ ~ ~~ _- - ~ & ~ ·_ &~ ~~ ~VV~ ~ ~~ ~11= ~ ' ~ ~ ~ ~ anew worlds primate have reproductive cycles shorter than the of the old world Species (I). For reproductive biology, the ~t extensively utilized Drew worlds Species are ,Saim~i sciureus (squirrel D~7S) and Cr~1lithrix jac~hus (ma~6ets)e m=,9h the folla~ir~ explanation of the mutual Cycle does not apply to rK!w world primates, the problems aviated with ovarian stimulation are- applicable. the i~mal Cycle lhe menstrual cycle of macaques is ally fair ~ in lath, being about Rally divided into folli~lar and lintel phases. Bring the second week of the folli=~lar phase, a circle follicle ATE grisly evident on one of the two ovaries; it continues maturation until madycle, when adulation arm transformation into a corms lu~ cxx~rs. He major endocrine events (see Figure 1) of the trial cycle are a gecxretric increase ~ peripilera1 An con~nt~tions of estradiol, Arching fern the maturing follicle, midcycle surges of Ill and F5H, irx~uced by the rising estradiol levels, and two ~ ; of pr ~ terone secretion face, the corpus luteum, a differentiated structure derived foul the ovulatory follicle. With diminished function of the corpus lubes, progesterone levels decline and menstruation occurs. additionally, a significant ~ ~ -pal FSH concentrations occurs in the last week of one cycle and continues thrcogh the first week of the folli=~1ar phase of the next cycle. Some reports have attributed the initiation of follicle Grog for the next circle to this rise in me An; (2) . _ ~ ~ · _ ~ ~ _~ ~ ~ cc ~~ ~ . The ~ interval for folli=~1ogenesis to occur ~ macaques is two weeks. If the periovulatory follicle is lyzed (3), the corpus later rove (3), or the trial Cycle s~ppr~ by pmg~s (4), the interval for new follicle growth is approximately two weeks ~ duration, equal in length to the follicular phase. However, it remains unknown f what folli=~lar stage follicle growth is initiated at the beginning of ~ 17 -
this too week interval - primordial, primary, secxrl~lry, or tlot:LLry (astral) follicles. Since an increase in mediumrsized antral follicles (0.5-l.Om~) occurs at the transition from one cycle to another, it is presumed that the ovulatory follicle develops from one of these mP~iumrsized antral follicles. The two week folli~lar phase has been divider into the intervals of recruitment, selection and ck~r~unoe. Recruitment Is the process By a Curt of follicles begins to matte, leadi~ to a follicle capable of avulati~. He size of the Art chasing this first week of the ~sbrual cycle remains Be. Stir the process of Election (appr~ima~=ly day 5-7 of the ~1 candle) the girdle follicle, Rich may lead to ovulation, be; bi~ica~ly distinct from all other follicles ~ bat ovaries. Finally, the pro= of ~ ina ~ e is the ~ i ~ by which the selec ~ follicle and its ~KXy===or, the corpus luteum, dictates the course of events ~ the hy ~ emus, the pituitary and ovaries. m e expression of dbllb}Lloe by the preovulatory follicle has been hypothesized to be achieved by the active secretion of an inhibitor of the development of other follicles (5), or, coincident with a diminished need for FSH support by the dknLL~ant follicle (2), the intuition of OH levels by es~actiol se~cic~n f m n this follicle, thus dinting available FSH for follicles requiring greater support than the dominant follicle. Irrespective of the r~ch~urism, it is evident that the dominant follicle precludes the development of other follicles daring the second week of the follic~1ar phase. Thus, by this second week, an asymmetrical ovarian function occurs In macaques; one ovary has ache primary game~enic role <3urir~ ache interval of the dominant follicle and the other ovary is f~ioni~ as an endocrine organ (5~. On fact, differential negative fed can FI;H secretion occurs beaten the ~ ovaries, wit the ovary ~~ the inant follicle having a Specific inhibition of ~ H secretion. obese concepts of recruitment, selection and dominance must be considered in planning treatments for the induction of folli~llogenesis. Such treatments most be initiated prior to the expression of dcruu~D,ce by the precvulatory follicle. Regulation of Follicul ~ enesis Both AH and FSH are required for sur~===ful follic`~ogenes~s. Nhmercus studies of episodic secretion of OH secretion have dk~T~:strated the association of hourly pull of TH with su~essfu] folli~1ogenes~ acuminating in ovulation and the at of such se retcry patterns with anavulation (6~. ~ini~ation of AH and reactant inn of Sue patterns of IN seareticn In monkeys with either arcuate Ales lesions (7) or juvenile stately (~) result; In the induction of ovulatory trust - :les. Incus, the ppisalic secretion of ~ a` - ars to be an integral cant of the processes r~ating-folli~1c~;~s. Ye patterns of AH secretion Reid for folli~1og~;is are less cafes. Perfuse of the larder circulating half-life of AH, Ponds or AH ink episodic patterns of FSH secretion are not as evident as those of Ill. Ye - ~ ~ ~
late luteal/~arly folli='lar phase increase ~ Huron F5H csrKY3ntrations has been proposed as the determinant of folli~1ogenes~s for the next ovulation (2~. moughFsH accretion during this interval to critics?` for normal folliculogenesis culminating in ovulation and normal lethal function, the specific increase in FSH which occurs during this transition from one cycle to another is not essential. Such a r.?~- dces not OrCU' prior to the first ovulatory cycle bullring sexual maturation, the first ovulatory cycle FxY~3xtrtum, nor during the folli~ar phase following repeated follicular destructions by cautery (9~. Thus, this elevation of ASH secretion ~ not essential for normal folli~llogenes~s culminating in ovulation. However, some degree of FSH secretion during this interval [c c~iti~1 for noun folli~llogenes=. Both inadequate ad Cod lueeal Cases have been described as spontaneously occurring In macaques (10~. E~bly, these luteal dysfunctions reflect aberrant folliallogenesis (111. In monkeys having these spontaneous luteal defects, FSH ~ntrati~s in the early folli=~lar Erase are below ache normal rare. Coveys treaty during the first week of the Dual Die with porcine folli~1ar fluid had a transient inhibition of ASH Otis; adulation was followed by aberrant lineal function, Ably induced by the Greasy AH concentrations In the early follic~1ar phase (12~. Thus, during the interval of normally elevate ~ I sea ration in the transition from one cycle to the next, FSH plays a significant role in the maturation of the developing follicle, but the elevation in FSH concentrations is not essential. Ovarian Stimulation Any treatment regimen designed to induce multiple follicular development most override a physiologic system operating to permit only a single follicle to mature to copulation. thus, taint Nat be initiated prior to the e~rgerxx of the danirent follicle. Additionally, the stimulation must not only pate follicular clevelc~ hat At also pride for normal devel~nt of granulosa arm ~ cells so that 1~ faction Is normal. E = r gonadotropic preparations in c ~ ination with Han * =rionic gc~LkJtno pin are each successful in inducing multiple folli='lar development: human menopausal gonadotropin (UPS Figure 2; 13), human follicle stimulating hormone (l4), pregnant mare's serum gYxeKkstrqpin (15), and porcine ESH (16~. Treatment with the=- gonadotropin preparations in combination with hog results in multiple follicular develc~nt and Adaption of meiosis ~t the Ocher. OF - #; may be aspirated fmn the follicles prior to 36 ham; post hoe or flub fed the soviet after 36 hairs; ~t ha; treatment. Ocx~e maturatic~ variable err] will range freon indenture (phrase I) Ash mature (database IT). Ye hot is typically a~inist~ after An estradiol corm ntratic~ns have achier at last 600 pg/ml. Rehash folli~lar development and oocyte maturation occurs with there treatment regimens, luteal function is not the same as in normal nY~s:rua1 cycles. PP-~U=- of the multiple folli=~1ar develcpment and correspondingly inr~1#lsed amount _ l] 9 _
of lute1 tissue following hCG treatment, pmg~tercrm Ratio are markedly greasy ~ the luteal phase of slime cycles relative t:o Be It's pycle (13~. Hover, despite ideas Procter Sties, the faction of the luteal tissue is diminish relative to normal t;=C~e. Following gonadotrc~i~ir~u~ ovarian st;~1atic~, ~ bit sites arx] IlI-bi=li~ site coupling to ache adenylate ~:la~ in are ~ (17~. lYpi~ly, Pugh net uniformly, 1H surges do no: for tin fin stimulated cycles, despite serum Rations of estradiol nonna1ly ass aviated with the irruption of IRISH surges. Scantly, ir~ibi1:ory products of the stimulated follicles block Be iti~f~c3: action of estradiol on I~/FSH sedation (18~. Be ovarian factor which blocks the positive f~ck action of estradiol has been refeed to as gonaclotr~p=-surg~ir~ibitir~ factor (GnSIF); whether GnSIF activity is due ~ a ~ clistinct freon Irvin remains to be detail (19~. : A proportion of mar~ceys treated with exagerx~us gonadotr~ins do have a spas If surge in rinse Deco ache rewire elevation of estractiol. Since Be ire reasing estrogen oorx~trations are due to Be collective production of estrogens, by a multitude of follicles, the degree of folli~lar maturation which has normally Purrs when ~=itive~ f~= occurs In the spontaneous cycles has not yet ~ ~ Prey stiumlated folliculogenesis. thus, when a spontaneous gonadatrop~n surge cars in a gonadotropin stimulated monkey, the surge is not Raze to folliallar maturation, resulting in premature luteinization of the gravelly with atter~nt inrush progesterone production (13~. me pr~ials station of pmgesterc)r~e pracl~: normal follim~1ar Veldt arm Ante maturation. Even among those subjects which do not have a premature Ill surge, there ~ a hetemgeT~s follim,Qar response to gonad~ropic stagnation. Typically' bash on estrogen rinse to gonadotmpic Estimation, the females have ret~:tively bad classified as "low", 'Sian" and 'high" rq~rs to gonadc~ic stimulation (20) . No Ethos has Ben developed for predicting the z~nse of a given subject to goradc~tr - ~ treatment. Be latter two problems (i.e., premature If surge and heter~s response to gc~nadatropins) can be ameliorated by adjuncti~re ~ era ~ with a gonadoLr~vin releasing hormone (GnRH) analog for the inhibition of endogenous gonadotrop ~ secretion (20). Agonists of GnEH, t initially pealing pituitary gonadakropin secretion will induce ~down-regulation" of pituitary function and inhibition of gonadotropin rep when administerel at a sufficient frequency and duration. Without the initial stipulatory phase, GnRH antagonists will imrPAR~t~ly inhibit gonadotrop ~ secretion. Simultaneous treatment with GnRH antagonist and exogenous gonadotropin will prevent the premature OH surge and will increase the response to exogenous gonadotropin. The estradiol response of 'tedium responders" Hal been observed to be greater with adjunctive antagonist treatment than without such treatment. - 120 -
AN sequela of ovarian stim~atic~n with qua dins the develc~rent of hyperprnlactinemia during to luteal phase of He ~imOa~ced Cole. math no present in all stim~la~ cues, this transi~t hyperprolactir~nia is prevalerIt when ~tr~ ~t~tians have been profanely elevated Uric the folli~1ar phase arm elevate id the luteal phase (13~. Quash ~tr~ me, fee hyperprolactinmia is not idol by the Hen milieu, but rather by Be syrwryistic Inaction of estrogen arx! progestin (21~. Firstly at least cue week of es~adiol <~ntrations In excess of 250 ~ is red for prig of the pituitary, follows by Austria estradiol Trains coincideic with progesteror~e levels at physiologic trations between 2 arm 4 ng/ml. In this ~1, hyperpr~lactin~ia ~3eve~q?s coincident with Be proges~ne elevation; estradiol or preserve alone do not irx~uce this hyp~prolactinemia. In Be stimulates Accrual cycles, these conditional pa err; of estradiol and pa - esterane will occasionally occur with attendant hyperprolactinernia. ~lems with Stimulated Ovarian Fashion As described above, the response to exoqenals ganadotr~in therapy maybe he~en~us, with varying degrees of folliallar develc~ and variable ~ maturation. Earl of this heterugenei~r Is due to Be endocrine milieu of the subject ardor the errs of a premature In surge. Additional variability may be Truce by He human c~orionic gonadotropin therapy administered to induce final folli~llar development and oocyte maturation. HCG has a long he f-life relative to EH. Follcr~ing the injection of ha; in monkeys, if follicles are net aspirated, but are permitted to ovulate, final follicular maturation continues for days and ovulations will I from 48 to 120 hours after hog treatment (22~. This response is probable due to hCG acting on a heterogenous population of follicles, with the least mature follicles at the top of hod treatment being those which ovulate last. Despite the problems with inducing follicular and oocybe maturation and management of the endocrine milieu, the greatest difficulty limiter r~ In primate folli~llogenesis and oogenes~s Is the availability of Sleazy subjects. Non-human primates are of a such Ore limited supply Han laboratory or domestic species. Allis Xylem ~1H ~ APT ~ · · · . . ~ ~ ~ a~ reach lZatlOn Of HIM subjects tor Ovarian sti~aticn prowls; hover, the gonadotropin preparations utilized at this tine are of human or n~primate origin, thus the treated irxlividu21s develop neutralizing annuities to the gonadotropin preparations (23, 24), precluding reutilization of the subject with the saIre gonadotropin pr~pezatic~n. Even if He immune recense togonadotropins did not cover, orc=~dbe bled, ethical considerations of how many ti~ chard a In primate be utilized In research protocols arm he many turgid Tours Child be perform weld benzene limiting factors;. gently, OCCUR; Hat be revered freon rx:,n-h~nan private= by either laparat~y or lab; ethical considerations encourage restriction of the - 121
performance of multiple surging procures on antes utilized ~ r~h. -thus, the limit availability of nonhuman primate=, he unavailab;li~ of non-h~n primate acnadc~r~ins, and the limit __ en, . _ do. . a _ ~ . a _ Ha ~ a . ~ ~ _ a reutilization of r~ subjects are' greater E~1eE; in he i~estigatic~n of folliallogenesis art oogenesis than are he biologic problems Aviated with irx~ucing follia~ar growth and axle maturation. ~ol~ic~ns for Emblems with Stimulated Ovarian Lice He variable ovarian Dense to gc~nado~z~ic '~i~1ati~ may be art corers by a~itianal rearm into the basic ~i~ r~ulatir~ folliallogenesis in nc~n-h~nan primates. NUT dices remain unanswered relative to primate follia~logenesis: a) Hat ~ the tine Curse for develc~rent of a primordial follicle into a periovulatory follicle? b) c) d) e) f) Cat stages of follia~ogenesis are gonad~rcp~n dependent? ~t are ache specific roles of ~ and PI;H? Is folli~1a~enesis a continues pro=, or can it be argots without atresia ooa~rring? During recruitment, Cat is the size of the c *Hart of follicles from which the dot follicle is selected? By what n~x~nism dog "selection" of the dominant follicle occur and how is dcminanm" of the periovulatory follicle sustained? When ovarian function is stimulated by exogenous gonadotro pies, what pool of follicles is responsive to this ~crea~nent? go How are oocybe and follicu1ar maturation inberl inked? h) Can mechanisms of follimllogenesis be extrapolated f``xll nonprimate species to printer? Estrogen race pbors have been demonstrated ~ the granulosa cells of rats (25); in ViVO' rat granulosa call proliferate following DEN treatment (26). In macaques, estradiol receptors have not been demonstrated in granulosA cells (27), and monkeys do not exhibit a granulosa roll proliferation when treated with DES (28). Thus, are reohanis=s of folliculogenesis different ~ primates then in non- primate species? Determination of answers to these questions will significantly Improve cur understanding of folliculogenesis and should allow for greater control of the folli~1ar response to stimulation regimens ~ th exogenous gonadotropins and more homogencus folli~1ar and oocyte responses. Additively, basic irn~estigations into oocyte maturation Laid prcF~ide critical insights reed for the c~veloE~nt of Bathes for the In vied maturation of Dotes. Ih,,~, when a heterogen~; distribution of opiates is obtained, the in~nature opiates can be mature in vitro to a Encage of ferti 1 inability. - 122 -
Me i2Tterlir~ prc~lems of no non-h~nan primate dins for ovarian sti~ndatio~ protocols, insane rinses to available Mains, and limiter supply of r~on-h~nan primate preset a scenario whim Is difficult ~ resolve. Were will rover be sufficient dandifies of ohms primate pituitaries or urine to allow for the p~ifica~ of Wins by cornrential technologies. C~11 lines are being premed by recombinant INA technology to prcx~uce non-h~nan primate ~ins. ~ever, it would seem highly unlikely that ~antiti~ of grants - m available or Scat of prelection wed permit the for~latic~n of pzepa~tians for repine ovarian stinn~Jation. Art alternative to the use of adds gonado~ins, is the augmentation of ~ fin ~ion. this can firstly be a~T~lishec] with the puisatile ~inis~tic~n of OH or clc~niphene citron tr`3at~nt, he the Free of Ovarian stipulation is not as extensive as concurs with exager~; adatropins, and the pulsatile a Ministration of GriPH is pa ~ lematic, and thus not practical for routine ovarian stimulation. Possibly, active (29), a member of the inhibin family which indurate= FSH secretion, may be ~ eful for ovarian stimulation. In the future, when its actions are understood and it is available, it or an agonistic analog may be fur An prorating ovarian stimulation. Of course, if the structure of activin is heter~gene~s between species, there inane response of recipient animals will be a problen. Evolving rational norm will clictate the appropriateness of reutilization of research subjects in multiple stimulation protons. Certainly, the Ned for suryir=1 recovery of dies can be eliminate ~ the fug by the continual improvers In the resolution of son~phy equipment. den resolution has bed significantly improved, Locates can be revved normal - idly by sor~raphica3ly guided pry. Iben the ethical ccmsideration will not be the perforate of multiple surgical pours, kilt ra~r the reutilization of Norman primates ~ multiple ovarian stimulation protocols e In statuary, relative ~ ache Utilization of non-h~nan primates in rearm on medically assisted conception, the major difficulties associates] with the stimmation of folliculogenes~s are not biologi - problems Assyrian winch the fiction of ache hy~halamic-pituitary- ovarian axis, but rather are managerial and logistical problems cabby by the limited availability of non-human primates, the unavailability of ncnrhuman primate gonadotrc pins for ovarian stimulation, and the ethical considerations of research subject reutilization. Thus, the majority of tonic science research on mealy assisted conception will need to be undertaken ~ laboratory or domesticated species and the non-human primate utilized for only selected studies. 123
A~I~ We a==istar~e of Martha Forester, Dara I~azy, and Patricia R - se In the preparation of grciEhics are We manuscript is sincerely ~r~ia~. - 124 -
~ c' ad ~ o o ~ oh en o ~ o on em o Ad c) v c) v ~ ~ o 0 v a, a' .# ~ 'A a) I - C ..... 1: ~ : + ~ . - ~ ~ is ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ - id. cO J (lu~/6n) HAS (Iw/6n) HE - 125 Figure 1 - O O O O 0 0 ~ CO _ (Iw/6d) o!pe~IS3 (lw/6u) o~oJelse6°~d _c~ on _ Cal _ - 0 _ ~ a' cD Q
a' at - · ~ - cn o cO ~ z ~ O ~ IL - lo O O O O O v O O 00 ~ ct so Cal ~ O O ~ 1~/5n HI o 0 o ~ ~ . ~ ~ o ~ A' on ~ ~ o _ = - ~ ~ o ~ Om o - ~ .=o o ~ ~ ~ ~ o a~ o ~ ~ - ~ 0 ~ ~ ~ , - ^ ~ ~ oo ~ ~ ~ ~ ~ v c) ~ ~ ~ ^~ - - 1 ~ ~ ~ ~ ~ 1 t ~ ~ s~ ~ ~ ~ ~ o a~ ~ ~ ~ ~ ~o c) cn a~ ~ 0 0 ~ 1 c l l l l l l l o o o o o o o o O CD C~ ~ '~ ~/6u H~1/90 \ I 1 1 1 1 1 1 1 1 1 o o C~ IUJ/6d 1°lP84S3 Figure 2 - 126 - ~ E o 0 cn - tl~ - c) lw~6u suo~Ise5°dd
~ENGF~ 1. merir~ MJ tl986) Ovarian ar~hito during follicle maturation. In: outlaw, WR arm J E:rw~ (ems) Repr~uctic~n arm Devel~nt Volume 3 of Comparative PriTrste Biology, Alan R. Li~c, ma:, Now York, p 215. 2. Zeleznik AJ arm SO Hillier (1984) The role of ganadc~tr~ins in the selection of me preovula~ry follicle. Clinical C~etrics arm Ecology 27 927 e 3. German AL, Em: Nixon, DK Johnson, and GD H - en (1977) P - ulaticnl of follialloger=;is in the cycling rhesus By: Selection of the dominant follicle. Endocrinology 100:155. 4 German AL arm GD Hodgen (1977) Systemic versus intraovarian pr~es- ter~ne replacement after Putty In rhesus Parleys: Differential patterns of gonadotropins art follicle growth. J Clin Erxiocrinol Myth 45:837. Goodman AL arm GD Hodgen (1983) The ovarian triad of the primate Anal cycle. Pant ~ Horm Res 39:1. 6. Cnxrley OF, M Filioori, D Spratt, and OF Santoro (1985) The p~y~;iology of gonadat~-releasing hormone (Grind static in men and women. Pant hag Horm R£s 41:473. Xhc~il E, ~ Plant, L WilOt, PE Beldhetz, arm G Call (1980) Neur~ocrine control of the rhesus Mornay dual cycle: Permissive role of the hypothalamic gonado~p~n-~l^~=ir~ hormone. Science 207: 8. Wildt L, G Marshall, arm E Knobil (1980) 1~peri~tal irx~uction of ply ~ ache infantile female rhesus monkey. Science 207:1373. 9. disarm AS, WE Nixon, artful GO Hodgen (1980) Sterile serum folliclfftimulating hormone elevations: Signifi~ In racrui~ am selection of the cock ant follicle err] ad of octopus 1lltelml normalcy. J Clill E~ldocrinol Match 50:1046. 10. William RF arm GD Hodgen (1982) the reproductive Cycle In fAge macaques. Aver J Prima=1 Suppl 1:181. U. di.Z~a, GS art GD Bergen (1981) ILL base dysfur~tic~n infertility: A sequel to a~rrar~c follies s. Fowl S~2:il 35:489.
12. Stouffer RL and GD Hodgen (1980) Induction of luteal phase defects in rhesus monkeys by folli~1ar fluid administration at the onset of the menstrual cycle. J Clan Endocrinol Mats 51:669. 13. Collins RL, RF Williams, and GO Hodgen (1984) Endocrine consequent es of prolonged ovarian hyperstimulation: Hyperp~ulactinemia, folli~1ar atresia, and premature luteinization. Fertil Sberil 42:436. 14. Supermen As, RF William, and GD Hodgen (1984) Ovulation iT~i~ using ''Ears'' follicle stimulating honoree in~eys. Fertil Ster 41:629. 15. Bavister, ED, BE Bowman, K Collins, DJ Diersc~ke, arm SG Finale (1984) Birth of rhesus Morley infant after In vitro fertilization and nonsu~ir=1 embryo transfer. Pax Natl- Acad Sol USA 81:2218. 16. Yano J and X~ Gould (1985) Suction of follicular grow In we squirrel monkey (Saimiri sciure ,~) with human rarity follicle stimulating hormone (Methodic). Fertil Steril 43:799. 17. Stuffer RL, GD Hodgerl, PE Grave=, DR Danforth, KM Eyster, are] JS Ott~bre (1986) Characterization of corpora lutea in Parleys after s~vulation with human menopa~~~1 gonadotropin or follicle stimulating hormone. J Clin E~ocrinol Metab 62:833. 18. Schenken AS and GD Hodgen (1983) Follicle-stimwlating hormone inured ovarian hyperstimulation In monkeys: Blockade of the luteinizing hormone surge. J Clan Endocrinol Met 57 50. 19. Danforth DR, MJ Sinosich, TL Anderson, CY Cheng, CW Bardin, and GD Hodgen (1987) Identification of gonadotrop m surge-inhibiting factor (GnSIF) in follicular fluid and its differentiation frill inhib~n. Biol Reprod 37:1075. 20. Hodgen GD, D Kenigsberg, RL Collins, and AS Schenken (1985) Selection of the dominant follicle and hormonal enhancement of the natural cycle. Ann NY Aca Sol 442:23. 21. Williams, RF, JG Gianfortoni, and-GD Hodgen (1985) Hyperprolactinemia insured by an estrogen-progesterone synergy: Quantitative and temporal effects of estrogen priming in monkeys. J Clin Endocrinol Batch 60:~96. 22. Alumni R. D Kenigsberg, D Danforth, RJ Falk, and GD Hodgen (1987) Cumulative ovulation rate in human mencpausal/ human chorionic gonadotropin-treat monkeys: ttStep-upll versus ttStep-d0wntl dose regimens. Fertil Steril 47:1019. 128
23. Platia MP, G B1~3uist, RF William, and GO HOdgen (1984) Refractoriness to gonad> therapy: How to distinguish Ovarian failure versus pse~arian rm;istan~x caused by r~lizirx3 ~i~ies. Ferry Ster; ~ 42:779. 24. Bavister BD, C I, and ED Schultz (1986) Refractoriness of Remus monkeys to r ~ ated Ovarian sting ration by edgers s gaoadotrc pins is caused by nonprecipitating antibodies. Am J Reprod Immun Micro biol Us:. 25. Richards AS, J~ Ireland, MC Rao, GA Bernath, AR Midgley, Jr., and LE Reichert, Jr. (1986) Ovarian follic`0ar devel ~ =~t ~ the rat: Hormone receptor regulation by estradiol, follicle stimulating hormone and luteinizing hormone. Endocrinology 99:1562. 26. Go1denberg RL, JL Vaitukaitis, and GT ROSS (1972) Estrogen and follicle stimulating hormone interactions on follicle growth in rats. Endocrinology 90:1492. 27. Hild-Petito S. RL Stouffer, NB West, and EM Brenner (1988) IDcal- ization of prcgesberone, but not estradiol receptors in folli~1ar and lethal tissues during the menstrual cycle. 70th anneal Meeting of the Endocrine ~ Cindy, Abstract #1121. 28. Koering M] (1987) Follicle maturation and atresia: Morphologic correlates. In: Stouffer RL (ed) The Primate Ovary, Plenum Press, New York., P.3. 29. Ling NP (1988) Isolation and characterization of gonadal polypepkidPc ~~ ~ . . . . . . In: anal regulate one secretion of follicle stimulating hormone. smidgen GD, Z Rosenwaks, and JM Spieler, EN ~ - · _ feds) Nonsteroida' Gbnadal R~ys~olog'~ Roles and Possibilities in Retractive LeveL~nt, Jones Institute Press, NorfoLk, USA. - 129 -
