Strengthening Research in Academic OB/GYN Departments (1992) / Chapter Skim
Currently Skimming:
6 A RESEARCH AGENDA FOR DEPARTMENTS OF OBSTETRICS AND GYNECOLOGY
6 A RESEARCH AGENDA FOR DEPARTMENTS OF OBSTETRICS AND GYNECOLOGY
Pages 141-228
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 141... ...
6 A RESEARCH AGENDA FOR DE~ARI~I~ OF OBSTETRICS AND GYNECOLOGY The previous chapters developed the themes Cat identifiable weaknesses exist ~ lhe OBJGYN research en~pnse and that actions to strengthen and support investigation she needed. This chapter dies research topics, the accomplishment of which would significantly Prove He health of women and He results of pregnancy.
|
From page 142... ...
~ their initial wow:, both panels emphasized the personal and social consequences of unsolved problems in these areas. The panel on reproductive biology and development highlighted seven arm, each of which in whole or in part covers topics that He coffee included ~ its research agenda: He con - 1 of reproductive fimction, infertility, conuac~phon, the molecular basis of embryonic development in animal and plant models, environmental factors affe~g reproductive biology and development, and postnatal growth.
|
From page 143... ...
The following sections were written by cod - e members, as acknowledged, and am in large part ~ on background papers prepared for Be co~inee, whose contributions are gIamfi~lly recognized (see Appendix C for a list of background pansy. 0~ and Follicular Development ~ the Oman' This section identifies areas of research - thin the broad field of ovarian Beckon that are best and most appropnately pursued in depar~ts of obstetrics and gynecology.
|
From page 144... ...
Migration of germ cells to their final location is accomplished prior to the fifth weelc of gestation. Whereas some chemotaxis is clearly ope~ationsI, the precise cellular mechanism or mechanisms uDderl~g the guidance of gem cells to the fur ovary remam uncmain.
|
From page 145... ...
~ CZ~nfication of the cellar origins of the somatic follicles cells-for exile, the steroid hor~ne producing ~nulosa and theca-mte~tidal cells surrounding He egg. There is r~on to believe that the germ cells may play a morphogenic role by inducing the appearance of Heir some tic counterpart.
|
From page 146... ...
16 fact, atredc follicles are r~der=1 incapable of ovulation. First noted ~ utero around month 6 of hum gestation, amnesia continues Irrupted throughout life, thereby resulting ~ relentless and Reversible Icon of the ovarian germ cell endowments It is noteworthy that He newbom human female enters life having lost as much as 80 percent of her egg cell endowment.
|
From page 147... ...
Clearly, if we could phonologically control and perhaps angst the process of Irma, premature ova failure might be successfully heated and the age of the menopause substantially delayed. Likewise~7 fe~lit:y objectives could be served by an Proved and augmented germ cell endowment.
|
From page 148... ...
This kind of investigation should yield elms as to how a follicle is selected "d Spared from aria Corpus Lute Function As intuiting as cell growth dig follicular development is Me cessation of cell gown Indoor cell death. G=nulosa cells divide on average only once following He preovulatoty LH surge and then differentiate into luteal cells.
|
From page 149... ...
In the absence of adequate information about the spatial and temporal p~uchon of these factors and their receptors in the ovary, however, such Ties am of limited value; Be findings rnny or may not be of physiological importance. The availability of sensitive molecular techniques such as ~ site hyb~idi7~don and reverse transcnption-polymerase chain reaction now makes it possible to accurately determine where and when the genes for growth factors "d their receptors are expressed in Be ovary.
|
From page 150... ...
Heparin, a product of mast cells, apes to play an important role in He actions of various growth factors. Proposed Research ouananfunaion.
|
From page 151... ...
Not only is there an a}~mdance of basic research topics ~ have important implications for solving problems of h amen fertility Ad infertility, but a better understanding of ova fimction would illusbate over normal and pathologic processes involving the regulation of cell growth "d differentiation in nanny over organ systems. The basic questions of physiology, cell growth, and differendaiion are relevant to mmy hut disease states ~ result in infertility and clinical annotations of ovanan Action.
|
From page 152... ...
6. The fusion of the sperm with the plasma membrane of the egg initiate the release of cortical granules, thereby casing the zone reaction and the release of the second polar body.
|
From page 153... ...
pla~ where Ah becomes Uncial with the inner aspects of the egg plasma membrane. There Is evidence that some of He cortical granules are relend prior to ovulation.
|
From page 154... ...
Continued investigation of the rnot/eaul' biology of spoon ~rornatin · Contin;ued investigation of the biod~errucal composition of cortical graham and the significance of cortical granule d~hiscence prior to Spm7? ,~gg fusion, as wed as their genera]
|
From page 155... ...
Such research draws on the techniques and methodologies of diverse disciplines including genetics, molecular and cell biology, and physiology. I Beers in decrements of OBJGYN should take the initiative in promoting the study of fetal growth and differenb~ation using the array of methodologies made available through modern science.
|
From page 156... ...
The spew of these events is illustrated by closure of the neural tube between 19 and 29 days of gestation and by development of the hem from the time of the Fist heartbeat at 21 days to its differentiation as a four~hambered puking organ by 56 days. Major malformations that can profoundly influence subsequent fetal growth and development are already established by Be end of He third fetal month, and it is dunog this period of time that major genetic Ed structural defects commonly result in pregnancy loss.
|
From page 157... ...
· Investigation of endocrine and growth factor signaling that modulmes fetal growth and organ maturation for example, the basis of actions of nwellerian inhibitory factor (~17;} and androgens in regulating sat d.ifferentiation. Fetal Growth and Placental Tramport The Bond Limiter of pregnancy is largely a period of growth and fimctiona1 refinement of organ systems Tut must be ~ to by He He of delivery.
|
From page 158... ...
Co~g~tal Infection and Substance Abme Congenital infections can also have profo~md influences on fetal growth and should be part of the dot of Fabric research. This arm includes veal infecHons such as cytomegalovirus disease, which is the most common congenital infection, and conditions such as congenital syphilis and toxoplasmosis.
|
From page 159... ...
· Development of new systems to deliver drugs, replacement honnone therapy, or nutrients to the fetus. Epideniol~ical R - earch There are conical epidemiology research oppo~ties for departs of OB/GYN in defining and following at-risk populations and also in clinical trials Evolving obs~ic patients.
|
From page 160... ...
After the intents of the fetal membranes is compromised, by whatever cause, preform labor commonly follows. If poem labor does not begin soon am membrane nature, infection by way of colonization by microorgams~s ans~g in the vagina or endocervix will precipitate preterm labor or else Men the fetus by way of fetal re~i~ato~y movements that cany Be infected ammodc fluid into the fetal lungs.
|
From page 161... ...
Much is known of the regulation of synthesis of these major Dominants of extracellular matrix formation and degradation In other dssues, but little or no info~ion is available concerning He fetal membranes. Proposed Research · Research must be directed to understanding the regulation of synthesis and degrn,1~,ion of the extrace~r mad of the fetal rn~ranes and contiguous decidua p~alis.
|
From page 162... ...
With limited family she, however, a larger proportion of tile obs~ic potion DOW is accounts for by won hang their Fist child; and In nulliparous women, the incidence of PIH is much greater dam in multiparous women. And wed respect to the major problems of pregnancy, for instance, maternal dead, fetal growth retardation, abn~ptio placenta, and so form, all forms of hypertension in pregnancy must be considered high-risk factors.
|
From page 163... ...
BE ~ normal pregnancy, He uterus reruns quiescent, acceptillg intrauterine distention to accommodate an S~ md baby, 1-2 pounds of placenta and fetal membranes, Ed 1 liter of Exotic fluid. Proposed Reseated' · Indignation must be assemblei1 to understand the fu;n~als of the maintenance of pregnancy and the spontaneous irutmion of pacrt~arition at term.
|
From page 164... ...
infection ~ some pregnancies appears to lead to He premah~ onset of labor. It is envisioned Cat colonization of fetal tissues (fetal membranes [~on Ed chonon laevel)
|
From page 165... ...
A large number of pregnancies that nominate in poem labor will be known to have pretelm centrical dilatation without apparent increase myometrial activity for days to weeks before the onset of active labor. And in some such cases, the preterm labor Is very prolonged; t~t is, slow Fecal dilation may continue with or without contracdons noted by the pregnant womb for days.
|
From page 166... ...
The obstetrician can appraise the potential role of infection, whether it occurs before or dig labor, in the parturitional prow. The obst~ic~ also is Cat sated to distinguish between pawned preterm labor and labor that does In fact eventuate In poem delivery.
|
From page 167... ...
D~pafun=ts of obstetrics and gynecology are in an almost Unique position to develop new cont~a~ptives since many young women seek advice from gynecologists for reproductive health care, mcl`'ding conbacephon. Thus, the gynecologist can study the desires of women and conduct appropnate clinical research into new contraceptive methods.
|
From page 168... ...
· Conduct and evaluate un~71ants in clinical trials. · Conduct long-term studies on NORP~ to deternune the health bends and risks of long~errn, loose, progestin~n~v contraception compared with combined oral contraceptives.
|
From page 169... ...
Dethrone how mum the hormone dose can be decreased without compronusing Electiveness and safety. · Perform spemalized phase 2 studies on CRs to drone whether vaginapy administered steroid are different from orally administered steroids wish resect to ovarian function; lipoprotein levels; mongolism; Elects on ceruc~l, uterine, and vag~n~ilpathology;and car}'oirydratemet~o~n.
|
From page 170... ...
1 1_~ ~ -=~~ - _~of~s~` -~of~~_~of~ am. ~ ~ ~ is ~- ~ ~ fade 1~ ~= ~ ~ _ a.
|
From page 171... ...
Proposed Research · Study the long-term consequences of OCs, and desire the rne~anism of action of Mellon In women.
|
From page 172... ...
Considerable evidence from both clinical trials and enema studies indicates Aft N-9 ~ microulc~ion of He vagina. This is of concern since epidemiological evidence suggests teal microulcmations increase susceptibility to HIV infection.
|
From page 173... ...
The halo approaches currently under investigadon use drugs that either act directly on male germ cells or withdraw their hormonal support. To date, all drugs Cat act directly on gum cells have tome effects and are relatively nonreversible, while hormonal suppression is readily reversible but is not as effective.
|
From page 174... ...
or fragments of this gonadotropin submit. (fly, We clinical trials are under way to evaluate venous forms of this conuacep~ve vaccine.
|
From page 175... ...
, and an end~ologist (for clinical trials)
|
From page 176... ...
Idendficadonof these c~nt;cal segments of the LH and FSH receptors offers an opporbJn~ty to interfere with hormone action by Using antibodies against these specific regions alone or in comb~hon with He LHRH antigen. The objective is to demons that imm~i7ntion win Pacific LH and FSH receptor segments will result in aeons of reproductive functions and induce a state of infidelity in experimental Denims.
|
From page 177... ...
Proposed Research · Identify an antiprogestin that can be used as a substitutefor RU 48~5 in a new medi=1 a~rtifament. Test cornlinations of an antiprogestin, anordrin analogs, progesterone Emphasis Inhibitors, and prostag~ins in pregnant animus to define the lowest creative dosages us terminating Pregnancy.
|
From page 178... ...
To achieve successfi~1 fer~i~ion, the male gang must be normal mid Factional, and He female oocyte must be properly Shoed by appropriate ovarian follicular development. Sperm motility is required to propel the sperm from the exocervix through the female reproductive tract to the ovarian follicle and the site of ferWi=:ioD.
|
From page 179... ...
After He developing embryo riches the Stunts, midway through the luteal phase, He proper sequence of implantation events must occur to Contain the growing pregnancy. Although ~lantadon of JO embryos has been well shed, we know ~ the reproductive events ~ he ~e, in many ways, vastly different from those ~ lower mammals.
|
From page 180... ...
Epidemiology Many wombs health issues are cloaked ~ emotion hetoric without sa~bstandating statistical support. An example is in Intro vermilion of which He public continue to be schemes ~ware, Ed at other times overly optimistic regarding the true success rates cunendy Edible.
|
From page 181... ...
The cervix is lined win a highly active secretory endo~elium that produces mucus in a hor~nally dependent fashion. Under the influence of circuladug estrogen, the cervical mucus becomes ~in, clear, and acellular allowing optima sperm motility and passage into the female genital tract.
|
From page 182... ...
fly, the hys~lpingogram provides ~adiologic i~onnadon on Cal patency, but Were are no tests to evaluate tubal Fiction. Such research is of tremendous importance given Me rapidly inc~mg incidence of ectopic pregnancy in the United States.
|
From page 183... ...
· The area of steroid and growthfa~or interactions with tubal epahek~m requires a major resend camera. · Normal implantation In the e~ometnum is moped by a namer of growth factors, and research into the role of growth factors in tubal function ma provide Tartan answers on the etiology and genesis of tubal ectopic pregnancies.
|
From page 184... ...
of hormonal treatment of various form of male subfertility, He role of mtraut~e and mtIa~rvical insemination in une~cpl~ed infe~litr, He necessity of, and the physiologic factors involved in, capacitation, and He acrosome reaction. The obvious coronary of a clew ~ders~anding of sperm fi~nchon would be the ability to develop new methods of contraception based on interfering with the normal ion process Proposed Research · Research at the basic science level most be inuia~ed before a Sue undemanding of the causes and possible treads of male infertility can be proposed.
|
From page 185... ...
In vitro F~ization and New Reproductive Technologies A den aver the first in vitro fertilization JVF) bit ~ 1978, Me number of stimulation cycles inidated in women for the purpose of embryo transfer ~ embed 25,000, despite its high cost (approximately SS,OOO per cycled and relatively poor success rate (14 percent for liv~bom infants)
|
From page 186... ...
· Research should be conducted on the involvement of growth factors, activation of the embryonic genuine, And metabolism in the any ears embryo. Premenstrual Syndrome The incidence of prem~1 syndrome (PMS)
|
From page 187... ...
There is a growing sense, however, that attempts to identify differences in He end~ology of the luteal phase of the cycle may have been relatively superficial, consid~g the likelihood Cat steroid metabolites are bioacEve and Rat Be bioachons of these metabolites as well as He steroid hormone precursor nary act by way of nongenomic processes. For equable, ~mb1 recently, the metabolic fam of the majority (60 70 percent)
|
From page 188... ...
in women and rhesus monkeys, 2 le~g to the conclusion Hat these hormonal patterns are the consequence of the pulsatile release of the hypothalamic decapep~de, gonadotropin-rel~ng ho~ne (GUARD, into the pituitary portal cumulation. This supposition has been ally verified by the direct measurement of this Peptize in pit:iit~uy portal blood of e~cpenmental mimals lending the He ~GnRH pulse generators to He news timing mechanism in He hypothalamus.
|
From page 189... ...
This can be psychogenic or stress induce ~2 16 the rhesus monkey, evm seemingly mild ~rbafions in He e~nment c" lead to angst of the GnRH pulse gene~asor.~3 A similar phenomenon c" be induced in such animals by He ~drninistrabon of He hypothalamic corticotropm-rel~g factor, an action Apparently mediated by endogenous opts - ;.l. Morphine itself is a potent inhibitor of GnAH pulse generator activit~r.ls The role of endogenous opines in the mediation of He rehouses to actual stress, however, is mill not entirely clear.
|
From page 190... ...
The electrophys~olo~cal atbs~ates of the GnRH pulse generator have now been identified and momtored in the rhesus monkey,2t the rat,22 and He goat.Z3 In there models, each LH pulse is imm=3i~ely Eyed by a burst of muld~t electrical activit y recorded from electrodes Planted in the mediocre h~othal~us. During He rhesus monkey menstrual cycle, these volleys of muldunit active last for about 2 minutes, whereas following ovanectomy their damson is some 15-20 minutes.
|
From page 191... ...
· lionize estr~iol can initiate the preov~ory gonadotropin surge in the absence of Ranges in GnRH production, what actual happens during the nonnal menstrual Gil is not known and should be investigated · lbe quantitative role of neuron deficits in the Saigon of infertility in women must be Dined · He mechanisms where 'stress. inhibits the GIRT pulse generator and consequent ovarian function must be elated Iheme*
|
From page 192... ...
Estrogen At is very elective in preventing hot flashes and in promoting grown of the ~agiDa1 epi~elium. It also is clearly established Act edged treatment of postmenopausal women sees to retard the loss of bone density and reduce the risk of myocardial infection.
|
From page 193... ...
Thus, there ale tony dam supportive of the belief that estrogen treatment of po~opau=1 women is salutary in the prevention of senior disorders of the skeletal and cardiovascular system and iD He relief of hot flashes and He cure of u~genim1 atrophy. It is established ~t estrogen At alone is ~ nik facb~r only for the development of endometrial carcinoma, and Cat this risk is low and He disorder is highly curable.
|
From page 194... ...
Therefore, gynecologists should matte a major effort to design and conduct research to define the optimum acceptable hormone treatment regimens for postmenopausal women. Proposed Research · Long-teTm, prospective studies to evaluate the effects and side affects of combinations of estrogen and progest~ns in the treatment of postmenopausal women should be conducted.
|
From page 195... ...
Thus, early menarche and lam men~e are Ink Cactus while oral conb~p~ve use appears to diminish the Ask. More ton half of Me cases of ovarian cancer are discover in an advanced stage.
|
From page 196... ...
A dose-re~onse relationship for ovarian cancer ~ chemotherapy treatment has been demonstrated and this provides a rationale for Me mbaperitoneal ~ministmion of the~utic agents. It also offers a route for other cell-specific therapies.
|
From page 197... ...
The b~s~holog~cal evaluation of endo~ial c:arcinoma for prognosis may be further refined by the determination of DNA content, proliferative index, steroid receptor exp~on, and He price of specific oncogene abnormalities. Hormone receptor status appears to be an important prognostic indicator.
|
From page 198... ...
Surgery remans the mainstay of it for endometrial carcinoma since most patients preset with clinical stage 1 disease. Adjunctive radiation therapy is resewed for patients win high risk factors that predict localfregional Hence.
|
From page 199... ...
The etiology of Scat cancer, par~cul~ly squamous cell carcinoma, has historically ~ associated ups multiple sexual partners, early age at the initiation of sexual activity, cigarette smo~g, and a history of sexually Witted diseases. Ibe effect of Lain dietary deficiencies as a risk factor for cervical dy~pla~ Is dell.
|
From page 200... ...
The stage of invasive cervical cancer mn~ir'~ Me single most important clinical prognostic indicator of S-year Oval. Approxinmt~ly oneself of cervical cancer patients with stage 1 disease {bat recurs after a radical hysterectomy have negative surgical margins and retropentoneal pelvic lymph nodes free of mmstaNc disease, indicating the need for better prognostic indictors.
|
From page 201... ...
2() 1 Do lIPV inflections require therapy tend if so, wash Apes airs net to reduce the frequency of cervical cancer?
|
From page 202... ...
The potential for fume use of chemoe~apy ~ so independent and combined modality of inept is sin;to the simadon dubbed with Local carcinomas. Proposed Research Clinical trials are needled to establish efficacy and surety of new tre~nents.
|
From page 203... ...
The MH-sponsored cancer and steroid hormone (CASH) study suggests a decrease ~ He relative risk of breast cane=, diagnosed ~ He 40s for women who have Aced oral contraceptives.
|
From page 204... ...
Proposed Research · What is the potential affect of oral contraceptives on pre- and posn? Ienopausal brat cancer?
|
From page 205... ...
Vim1 STDs including hut immunodefic~ency ~ (HIV) , genital herpes simplex (HSV)
|
From page 206... ...
Although an interdisciplinary approach involving microbiology, immunology, ge~edCS, and molecular biology will be needed to meet some of these challenges, obstetrics and gynecology because obstetrics and gynecologists are among the primary providers of health care for women-will have to play a major role in meeting these challenges, particularly in relation to epidemiologic studies and clinical trials. Prevent Sexually Emitted Diseases by Developing Clinically Effective and Safe Vaccines The structural components of STD orgasms have bean intensively analyzed and dissected, providing info~on for a miorm1 approach to vaccine development that An be Quiz to prevent f~er infections.
|
From page 207... ...
· The mucosal immune response lo organisms that cause SlDs is Optical for the development of successful vaccines, whim my simulate both Be and Tcell Iambs of the immune response Consequently, detailed mapping and analysis of the Epitomes of the proteins associated with SID orgasms in en citing immune response are necessary. · The mucosal fine system of the hunk fake genital tract and us role in the prevention of infection andlor susc~tibilRy to infection should be studied more intensely.
|
From page 208... ...
Investigate the satiety and efficacy of e~=im~al antiviral drugs against HIV and treatment of opportunistic infections in both pregnant and nonpregnant women. · Evaluate the Efficacy of treannent regions for pelvic inf~urwory disease in relation to preservation of noons reprobative function Ibis win require a long-term multicenter trial to adequately assess long-term outcomes.
|
From page 209... ...
Develop an unhanding of the nature of p~h~gen-cell interactions, especially onus Awakens and entry, in order to formulae effective strategies for insertion of transnussion. Natural history studies of NPV infection and the influence of the ~ruruum system are critical unportant in adepts to prevent the development of cervical cancer.
|
From page 210... ...
=r~ms that influence progression of HPV infection to anogenitadl neop~asia. Urgently ne~l are HPV natural history studies that examine the roles of Oral He and immune status.
|
From page 211... ...
· Identify behavioral risk factors; this wow would be facilitated by a national survey of sex be7mvior.
|
From page 212... ...
n rates for Sons, and conduct natural history studies for disease progression in specific, wed - haractenzed positions. · Hey the psychosocial need of HlV-positive women and their family systems f~r~itional and nonrational, including lesbian women)
|
From page 213... ...
Balker T.G. A quan~a~c ~ cytological Rudy of germ cells in he ones, Proc R Soc (Biol)
|
From page 214... ...
1989. Expr~on of basic fibrobl~ grown factor in the rat ovary: Detection of LANA ~ rc~c~c acre o~olymc:asc chain reaction.
|
From page 215... ...
19~. Pen~c h~o~ Cow ~ hamster ~ mouse eggs fcnilized wad mouse sperm.
|
From page 216... ...
ant Uadawood, L.E.: Ef~cct of matcr~al f~iDg on fetal g=wth, serum, i~litc growth factors (IGF's) , aDd d~c IGF me~ger nbonuclcic acids EDtocnnology.
|
From page 217... ...
Clin 74:27~286, 1984. Uzan, S., Beaufills, M., Brawl, G., Am, B., et al.: Pre~rcDtion of fetal growth retardation with low~osc amp: F - lags of Tic EPREDA trial.
|
From page 218... ...
218 Cot SWING RZ:SELECH IlI~IC OB/~DEP~ Bardin, C.W.: NORPLANT comraccpti~c ~lams. Oln~tArics Ad Gynecology Report 2:96 102, 1990.
|
From page 219... ...
Circho~al oscillators of plum LO lores ~ the ovanec~ed rhesus monkey. EDdocri ology 87: 850, 1970.
|
From page 220... ...
Suclding and thc coD-1 of gonadotropin secretion. Ir~: lAc Pkysiology of ~tcp~od~aon.
|
From page 221... ...
pulse gcac~tor phasic electrical activity ant the d~cs of lutein~ hormone (by) pulses us the rhesus monkey.
|
From page 222... ...
Br J Obstet Gynecol 94:202-7,1987.
|
From page 223... ...
lIormo~al trcatmc~t of endoKtriaI carcinoma: an o~crview and new dc~rclopment ~ biology. J Steroid Biochem Mol Biol 37:997-1001,1g90.
|
From page 224... ...
Amer J Obstet Gynecol 164:424,1991. Namcll A, Roger V, Naisell M
|
From page 225... ...
Stim~tory and inhibitory groove factors am bow cancer J Steroid Biochem Mol Biol 37:6795~03,1990. ForDantcr T
|
From page 226... ...
Gynecol Oncol 23:87, 1986. Yordan EL Jr, Schlac~ J, Geddis O ct al.
|
From page 227... ...
ICY UGLY FOR OB/G=D~ Sentry Tr~4Ad Is Nat - ~ of - ~ ~ - ~ - s I: Icy T~ ~s Roth Pam, Ns6~ ~ of Ha, arc, Md.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.