Original Article
A Preliminary Report on Oocyte Donation Extending Reproductive Potential to Women over 40
N Engl J Med 1990; 323:1157-1160October 25, 1990
- Abstract
- Abstract
Background.
Fertility in women 40 years of age or older is decreased, and in those with ovarian failure it is thought to be irrevocably lost. The donation of oocytes to young (<35 years old) women with ovarian failure has allowed many considered infertile a chance to become pregnant. In these women gonadal hormone replacement results in an endometrium receptive to implantation. It is not known whether the endometrial response to such replacement is decreased in women over the age of 40.
Methods.
To test the efficacy of oocyte donation to older women, we enrolled seven women 40 to 44 years old with ovarian failure in a trial of hormone replacement and embryo transfer, using oocytes obtained from women undergoing ovarian hyperstimulation solely for gamete donation.
Results.
Seven stimulated cycles in the donors that were synchronized with nine cycles in the recipients resulted in eight embryo transfers. Five viable pregnancies were established, one with twins. A sixth pregnancy ended in miscarriage. Five normal infants were delivered by cesarean section, and one stillborn infant was delivered vaginally. The outcomes were compared with those in women under the age of 40 with ovarian failure who were also participating in our donor-oocyte program and in infertile ovulating women 40 or older who were undergoing standard in vitro fertilization. No significant differences in rates of implantation or ongoing pregnancy were noted in older women as compared with younger women receiving donated embryos. These rates, however, were higher than the rates in the infertile ovulating women of similar age who were undergoing standard in vitro fertilization.
Conclusions.
These preliminary results suggest that the endometrium retains its ability to respond to gonadal steroids and provides a receptive environment for embryo implantation and gestation even in older women. (N Engl J Med 1990; 323:1157–60.)
Article Activity
- Article
FERTILITY in women over the age of 40 is generally acknowledged to be decreased. In analyzing a large series of women, Leridon suggested that fecundity in women actually begins to decline by 30 years of age.1 Fertility rates peak by the age of 25 and fall throughout the remainder of reproductive life. Although many in vitro fertilization programs accept women over 40, the pregnancy rates in such women have been reported to be decreased,2 and the rates of miscarriage may be increased.3 Fertility is similarly diminished in older women undergoing donor insemination.4 In them, the cumulative success rates for pregnancy fall after they reach 30 years of age and decline dramatically after age 35.5
As many as 10 percent of women have ovarian failure by 40 years of age,1 and until recently these women were considered to be hopelessly infertile. With aging, diminished fertility is believed to occur principally as a result of oocyte senescence, but it could also be due to resistance to implantation of the embryo in the endometrium.2 After implantation, the loss of pregnancy is also increased in women over 40, presumably as a result of a combination of detrimental changes in aging oocytes and the endometrium.
We previously reported the establishment of a program involving the nonanonymous donation of oocytes.6 Initially, younger women provided oocytes to women under the age of 40 with ovarian failure. The donors were fertile women who underwent controlled ovarian hyperstimulation and transvaginal, ultrasound-directed aspiration of oocytes for the sole purpose of donation. Thirteen cycles were initiated, resulting in 11 embryo transfers and 6 ongoing pregnancies. Encouraged by our preliminary experience, we expanded the protocol to include women over the age of 40 with ovarian failure who were otherwise in good physical and psychological health. In this article we report the results of our initial trials of oocyte donation in these older patients. Since the oocytes were donated by a group of young, fertile women, we could determine whether age alone affects the receptivity of the uterus to embryo implantation.
Methods
Between February 1, 1989, and September 1, 1989, seven infertile couples consented to undergo at least one cycle of in vitro fertilization with donated oocytes. All the recipients were married women 40 to 44 years old who had previously been found to have primary ovarian failure. In all the women, the ovarian failure was considered to be idiopathic and had occurred at least two years before enrollment in our study. All the women had serum follicle-stimulating hormone values above 100 IU per liter and estradiol levels below 90 pmol per liter. There was no attempt to induce ovulation in these women because of the long-standing and severe nature of their ovarian failure, as demonstrated by their very high levels of follicle-stimulating hormone.
None of the women had any major medical problem. The couples and donors were also interviewed by a psychologist before study entry and deemed acceptable candidates for embryo donation. The couples were advised of the possible increased obstetrical risks in pregnant women over the age of 40.7 Individual consent forms were signed by the donors, the recipients, and the recipients' husbands. The protocol for embryo donation had been reviewed and approved by the institutional review board of the California Medical Center, Los Angeles.
The women with ovarian failure were treated with oral micronized estradiol and intramuscular progesterone as previously described (Fig. 1Figure 1
Regimens of Ovarian Stimulation and Hormone Replacement Used to Synchronize the Development of Ovarian Follicles in the Oocyte Donor and the Endometrial Cycle in the Recipient.).8 The medications were administered in divided doses and taken twice daily, except that estradiol was taken in three doses on the days when the dose was 6 mg. After this regimen of hormones, a histologically normal endometrial biopsy specimen was obtained from each recipient on day 26 of a simulated replacement cycle within two months of the embryo-transfer cycle.All the women receiving embryos had a normal endometrial cavity, as determined by hysterosalpingography, as well as a normal mammogram, electrocardiogram, and fasting blood glucose concentration, and a negative serologic test for human immunodeficiency virus (HIV) infection. Blood type and Rh status were also determined. The husbands of the recipients also had negative tests for HIV infection and negative semen cultures.
The oocytes were provided by three fertile women 31 to 34 years old who were paid $1,500 per cycle by the recipients. Each had regular ovulatory cycles, no gynecologic abnormalities, and no major medical or psychological illness. Because of the large number of oocytes retrieved from one of these donors during a previous stimulated cycle,9 her ovarian hyperstimulation cycle was synchronized on two occasions with the cycles of two recipients. The donors underwent controlled ovarian hyperstimulation with use of subcutaneous leuprolide acetate (1 mg daily) and intramuscular human menopausal gonadotropin (three ampules daily) as previously described.6 Leuprolide was begun during the mid-luteal phase of the donor's menstrual cycle. Human menopausal gonadotropin was begun once the donor's serum estradiol level fell below 90 pmol per liter. Ultrasound-directed transvaginal aspiration of follicles was performed under intravenous sedation 36 hours after the intramuscular administration of human chorionic gonadotropin. The recovery of oocytes, fertilization, embryo culture, and subsequent transfer of the embryo were performed by standard methods of in vitro fertilization currently used in our program and described previously.6 All transfers of embryos were performed transcervically, without anesthesia.
The recipients began receiving estradiol replacement three days before the donor began receiving human menopausal gonadotropin and then started progesterone replacement on the morning the donor received human chorionic gonadotropin (Fig. 1). The day progesterone replacement began was arbitrarily designated as day 15 of the simulated cycle. The embryos were transferred on day 18 of the cycle. Pregnancies were confirmed by the measurement of serum levels of the beta subunit of human chorionic gonadotropin and by transvaginal ultrasonography. Individual implantations were verified by the presence of a distinct gestational sac on ultrasonography. Clinical pregnancies were confirmed by visible heartbeats within the gestational sacs at least eight weeks after the transfer of the embryo. All the women who became pregnant continued to receive 2 mg of estradiol orally and 100 mg of progesterone intramuscularly in daily divided doses for an additional 100 days.
The outcomes in the group of recipients were compared with those in two other groups in our in vitro fertilization program. The first group (n = 9) was composed of all the women under 40 with primary ovarian failure who had participated in the donor-oocyte program since its inception. The mean age in this group was 32 years (range, 27 to 39). The second group (n = 22) consisted of all ovulating but infertile women 40 or older (mean, 41) who participated in our standard program of in vitro fertilization from January 1987 through August 1989. Women undergoing ovarian hyperstimulation received either human menopausal gonadotropin (initial dose, 225 IU a day) followed by human chorionic gonadotropin (10,000 IU) when the follicles were mature, or leuprolide acetate and then human menopausal gonadotropin (225 IU a day) followed by human chorionic gonadotropin (10,000 IU) when the follicles were mature. We performed transvaginal aspiration, gamete and embryo culture, and transcervical transfer of the embryo, using the same gamete laboratory and personnel as previously described.6
The numbers of oocytes obtained, fertilized, and transferred and the rates of implantation and pregnancy were compared in the three groups. The differences between groups were analyzed with either the nonparametric Mann—Whitney test or Fisher's exact test, as appropriate. A P value of less than 0.05 was considered to indicate significance.
Results
Table 1Table 1
Results of the Transfer of Fertilized Donor Ova in Women 40 or Older with Ovarian Failure. shows the outcomes of each of the cycles in the seven women 40 or older who received embryos. Five women underwent one cycle and two underwent two cycles. Six pregnancies resulted from eight transfers of embryos to these women. In one instance no transfer was performed because there was no fertilized oocyte. A total of 28 embryos were transferred during the eight transfers (mean [±SD], 3.5±1.1 embryos per transfer). Ten implantations resulted, for an implantation rate of 36 percent. Six of the seven women became pregnant. One pregnancy ended in a miscarriage after nine weeks of gestation. In one woman the pregnancy progressed normally, but the fetus died in the uterus after 40 weeks of gestation; no cause of stillbirth was apparent. The pregnancies in the other four women were normal, and they all delivered normal infants.Table 2Table 2
Results of the Transfer of Fertilized Donor Ova in Women 40 or Older with Ovarian Failure, as Compared with the Results in Women under 40 with Ovarian Failure and Those of Women over 40 Undergoing Standard in Vitro Fertilization (IVF) and Embryo Transfer.* shows the results in the patients with ovarian failure who were 40 or older as compared with those in the younger patients with ovarian failure in our oocyte-donation program and those in the infertile ovulating women 40 or older who were undergoing ovarian hyperstimulation and oocyte aspiration in our in vitro fertilization program. There were no significant differences in outcome in the older as compared with the younger women with ovarian failure. Among the older women who underwent standard in vitro fertilization and embryo transfer, significantly fewer oocytes were retrieved, fewer embryos were transferred, and the rates of implantation and pregnancy were lower than in either the younger or older women who received donated embryos.The overall rate of oocyte fertilization in the older women with ovarian failure was 41 percent (40 of the 97 oocytes retrieved). This was lower than the overall rate of fertilization (62 percent) among couples without male-factor infertility in our general in vitro fertilization program in 1988 (data not shown; P<0.05). The husbands of 2 of the 7 women in the study group, as well as those of 6 of the 22 infertile ovulating women who were 40 or older, were suspected of being infertile on the basis of abnormalities in their screening laboratory examinations (0 percent score on the hamster penetration assay). The rate of fertilization was lower in both groups than in the group of women with ovarian failure who were under 40, none of whose husbands had such abnormalities. The poor rates of fertilization in two women (Patients 3 and 5) contributed greatly to the low overall rate. Despite poor fertilization rates in these two (0 of 10 and 2 of 10 oocytes in Patient 5, and 1 of 21 oocytes in Patient 3), when fertilization occurred the zygotes cleaved, implanted, and continued to develop in both cases, and the pregnancy was successful in Patient 3.
Discussion
Ovarian failure occurs in most women in the United States between the ages of 48 and 51.1 , 10 Many women are either menopausal or perimenopausal by the time they reach their early forties. For women who delay childbearing until late in their reproductive lives, the likelihood of starting a family is decreased. For those with ovarian failure there are few options for pregnancy.
We have previously demonstrated that high rates of pregnancy can be achieved in women with premature ovarian failure if multiple embryos are transferred to them after hormonal stimulation of the endometrium.6 The rate of pregnancy in such women is approximately three times that reported by the national registry for infertile ovulating women who undergo standard in vitro fertilization and embryo transfer.11 We believe that the increased rate of embryo implantation results both from the receptive uterine environment artificially created in these recipients and from the transfer of multiple embryos from oocytes obtained from young, fertile donors.
The endometrium of women with ovarian failure can be made histologically normal with a combination of oral micronized estradiol and intramuscular progesterone.8 Endometrial-biopsy specimens from women receiving this hormone replacement regimen (both those under and those over 40) are histologically indistinguishable from normal endometrium. We therefore believed that in older women with ovarian failure a pregnancy rate similar to that of younger women with the same problem was possible, provided that embryos of similar quality were transferred. Indeed, the rate of implantation (36 percent) in this older group was not different from that previously reported by us in women under the age of 35 (35 percent).12
The incidence of genetic anomalies in the offspring of women undergoing in vitro fertilization and embryo transfer is not different from that in the population at large.11 Whether the incidence of such anomalies in this older group of women with ovarian failure will resemble that of the younger donors who provide the gametes or that of their own age group is a matter of speculation. The increased incidence of anomalies in the offspring of older women in general may be due to either the older gametes or lack of rejection of abnormal conceptuses by the endometrium of older women. Similarly, the rate of miscarriage in these older women is not yet known, but our results suggest that it is not different from that of younger women in the general population.
The obstetrical risk to the women in this study is unknown. However, infant mortality in women 40 or older is significantly increased (12 deaths per 1000 live births at age 40 vs. 9 per 1000 at age 30).13 Maternal mortality rates are also higher (80 per 100,000 live births at age 40 vs. 20 per 100,000 at age 30).14 If high-risk obstetrical care is provided, the rate of obstetrical complications may not be appreciably higher than that in younger women.15 Careful screening of patients will further lessen complications if those with known high-risk factors, such as hypertension, diabetes mellitus, or thromboembolic disease, are excluded from participation. Since the risks are currently unknown, all women should be carefully screened and counseled regarding pregnancy before oocyte donation is attempted.
Oocyte donation provides older women with ovarian failure a reasonable chance at achieving pregnancy. To those with existing ovarian function, conventional in vitro fertilization and embryo transfer may still be offered, although the success of pregnancy is probably reduced and at best results in a live-born child in less than 10 percent of the initiated cycles.2 A recent report suggested that the creation of a functionally agonadal state by means of pituitary down-regulation with a gonadotropin-releasing hormone agonist followed by ovarian hormone replacement allows the cycles of selected women with ovarian function to be synchronized with those of an oocyte donor.16 Such a protocol may be applicable to women whose ovarian failure is intermittent, as is often the case in perimenopausal women.
In this small series, the rates of pregnancy with donated oocytes in women with ovarian failure who were 40 or older approximated that in younger women in the same program, demonstrating that receptivity to embryo implantation can be maintained if not enhanced by hormone replacement therapy in such older women. The probability of randomly achieving pregnancy in women with ovarian failure in this age group with any other existing method is extremely low. Since women in this age group with functioning ovaries are considered appropriate candidates for infertility treatment, it seems appropriate that those without ovarian function should also be allowed a chance to experience pregnancy if they desire it.
Source Information
From the Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Southern California, Los Angeles. Address reprint requests to Dr. Sauer at Women's Hospital, 1240 N. Mission Rd., Rm. L946, Los Angeles, CA 90033.
- References
References
1
Leridon H. Human fertility: the basic components. Chicago: University of Chicago Press, 1977.
2
Edwards
CrossRef | Medline3
Romeu
Web of Science | Medline4
Fédération
Full Text | Web of Science | Medline5
Virro
Web of Science | Medline6
Sauer
Web of Science | Medline7
Kajanoja
Web of Science | Medline8
Sauer 9
Sauer
Web of Science | Medline10
Mishell DR Jr. Menopause. In: Droegemuellar W, Herbst AL, Mishell DR. Stenchever MA, eds. Comprehensive gynecology. St. Louis: C.V. Mosby, 1987:1082–107.
11
In vitro fertilization/embryo transfer in the United States: 1987 results from the National IVF-ET Registry . Fertil Steril 1985; 51:13–9.
12
Paulson
Web of Science | Medline13
Friede
Web of Science | Medline14
Rochat
Web of Science | Medline15
Kirz
Web of Science | Medline16
Meldrum
Web of Science | Medline
- Citing Articles (52)
Citing Articles
1
Eric J. Forman, Nathan R. Treff, Richard T. Scott. (2011) Fertility after age 45: From natural conception to Assisted Reproductive Technology and beyond. Maturitas 70:3, 216-221
CrossRef2
Dieter Egli, Hidenori Akutsu. (2011) Aging of the Female Reproductive System. Journal of Mammalian Ova Research 28:3, 118-125
CrossRef3
Q. F. Cai, F. Wan, R. Huang, H. W. Zhang. (2011) Factors predicting the cumulative outcome of IVF/ICSI treatment: a multivariable analysis of 2450 patients. Human Reproduction 26:9, 2532-2540
CrossRef4
Jaime M. Knopman, Sheeva Talebian, Alan S. Berkeley, James A. Grifo, Nicole Noyes, Frederick Licciardi. (2010) Fate of cryopreserved donor embryos. Fertility and Sterility 94:5, 1689-1692
CrossRef5
Richard J. Paulson. 2010. Oocyte Donation and Third Party Parenting. , 464-467.
CrossRef6
Alex J Polotsky, Nanette Santoro. 2008. Uterine disease in midlife and beyond: the menopausal transition and postmenopause. , 785-796.
CrossRef7
O Djahanbakhch, M Ezzati, A Zosmer. (2007) Reproductive ageing in women. The Journal of Pathology 211:2, 219-231
CrossRef8
Anne Z Steiner, Richard J Paulson. (2006) Oocyte Donation. Clinical Obstetrics and Gynecology 49:1, 44-54
CrossRef9
Mark V Sauer, Suzanne M Kavic. (2006) Oocyte and embryo donation 2006: reviewing two decades of innovation and controversy. Reproductive BioMedicine Online 12:2, 153-162
CrossRef10
(2004) Oocyte donation to postmenopausal women. Fertility and Sterility 82, 254-255
CrossRef11
BASIL C. TARLATZIS, LEONIDAS ZEPIRIDIS. (2003) Perimenopausal Conception. Annals of the New York Academy of Sciences 997:1, 93-104
CrossRef12
F. Ubaldi, L. Rienzi, E. Baroni, S. Ferrero, M. Iacobelli, M.G. Minasi, F. Sapienza, F. Martinez, L. Cobellis, E. Greco. (2003) Implantation in Patients Over 40 and Raising FSH Levels—a Review. Placenta 24, S34-S38
CrossRef13
Lawrence M Nelson, Vladimir K Bakalov. (2003) Mechanisms of follicular dysfunction in 46,XX spontaneous premature ovarian failure. Endocrinology & Metabolism Clinics of North America 32:3, 613-637
CrossRef14
Lubna Pal, Nanette Santoro. (2003) Age-related decline in fertility. Endocrinology & Metabolism Clinics of North America 32:3, 669-688
CrossRef15
Sanja Kupesic, Asim Kurjak, Drazena Bjelos, Sanja Vujisic. (2003) Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age. Fertility and Sterility 79:1, 190-197
CrossRef16
Chih-Chi Chuang, Chin-Der Chen, Kuang-Han Chao, Shee-Uan Chen, Hong-Nerng Ho, Y.u-Shih Yang. (2003) Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization. Fertility and Sterility 79:1, 63-68
CrossRef17
Santiago Brugo-Olmedo, Claudio Chillik, Susana Kopelman. (2001) Definition and causes of infertility. Reproductive BioMedicine Online 2:1, 41-53
CrossRef18
Santiago Brugo-Olmedo, Claudio Chillik, Susana Kopelman. (2001) Definition and causes of infertility. Reproductive BioMedicine Online 2:1, 173-185
CrossRef19
JENNIFER A. PARKS. (1999) On the Use of IVF by Post-menopausal Women. Hypatia 14:1, 77-96
CrossRef20
MATTHEW A. COHEN, MARK V. SAUER. (1998) Fertility in Perimenopausal Women. Clinical Obstetrics and Gynecology 41:4, 958-965
CrossRef21
BRADFORD L. BOPP, DAVID B. SEIFER. (1998) Oocyte Loss and the Perimenopause. Clinical Obstetrics and Gynecology 41:4, 898-911
CrossRef22
Steven D Spandorfer, Maureen Moomjy, Owen K Davis, Larry I Barmat, Ina Cholst, Zev Rosenwaks. (1998) Oocyte donation: does a previous attempt affect a subsequent attempt?. Fertility and Sterility 70:2, 222-226
CrossRef23
Kurt Barnhart, Joseph Osheroff. (1998) Follicle stimulating hormone as a predictor of fertility. Current Opinion in Obstetrics and Gynaecology 10:3, 227-232
CrossRef24
Hossam I. Abdalla, Anne Billett, Andrew K. S. Kan, Sabah Baig, Marie Wren, Lena Korea, John W. W. Studd. (1998) Obstetric outcome in 232 ovum donation pregnancies. BJOG: An International Journal of Obstetrics and Gynaecology 105:3, 332-337
CrossRef25
Edward H. Illions, Michael T. Valley, Andrew M. Kaunitz. (1998) INFERTILITY. Medical Clinics of North America 82:2, 271-295
CrossRef26
Mark V Sauer. (1998) Motherhood at any age? Egg donation was not intended for everyone. Fertility and Sterility 69:2, 187-188
CrossRef27
MARK V. SAUER. (1997) Infertility and Early Pregnancy Loss Is Largely Due to Oocyte Aging, Not Uterine Senescence, as Demonstrated by Oocyte Donation. Annals of the New York Academy of Sciences 828:1 Uterus, The, 166-174
CrossRef28
ANDREA BORINI, CARLO BULLETTI, MONICA CATTOLI, LUCIA SERRAO, VALERIA POLLI, STEFANIA ALFIERI, CARLO FLAMIGNI. (1997) Use of Recombinant Leukemia Inhibitory Factor in Embryo Implantation. Annals of the New York Academy of Sciences 828:1 Uterus, The, 157-161
CrossRef29
(1997) Oocyte donation to postmenopausal women. Fertility and Sterility 67:5, 2S-3S
CrossRef30
Mary T. O'Rourke, Susan F. Lipson, Peter T. Ellison. (1996) Ovarian function in the latter half of the reproductive lifespan. American Journal of Human Biology 8:6, 751-759
CrossRef31
Marinko M. Biljan, Clare T. Taylor, Christine M. Gosden, Simon V. Jones, Christine G. Malone, Charles R. Kingsland. (1995) How acute is the acute shortage of oocyte donors in the UK? Results of a British National Survey. BJOG: An International Journal of Obstetrics and Gynaecology 102:9, 746-747
CrossRef32
Joseph G. Schenker. (1995) Sperm, oocyte, and pre-embryo donation. Journal of Assisted Reproduction and Genetics 12:8, 499-508
CrossRef33
Yoshiteru Terashima. (1995) PREFACE. Asia-Oceania Journal of Obstetrics and Gynaecology 21:1, 57-57
CrossRef34
Richard S. Legro, I.Lame Wong, Richard J. Paulson, Rogerio A. Lobo, Mark V. Sauer. (1995) Recipient's age does not adversely affect pregnancy outcome after oocyte donation. American Journal of Obstetrics and Gynecology 172:1, 96-100
CrossRef35
DOMINIQUE DE ZIEGLER, RENATO FANCHIN, MARC MASSONNEAU, CHRISTINE BERGERON, RENÉ FRYDMAN, PHILIPPE BOUCHARD. (1994) Hormonal Control of Endometrial Receptivity.. Annals of the New York Academy of Sciences 734:1 The Human End, 209-220
CrossRef36
JEROME H. CHECK. (1994) The Use of the Donor Oocyte Program to Evaluate Embryo Implantation. Annals of the New York Academy of Sciences 734:1 The Human End, 198-208
CrossRef37
Odile Frank, P. Grace Bianchi, Aldo Campana. (1994) The end of fertility: age, fecundity and fecundability in women. Journal of Biosocial Science 26:03,
CrossRef38
Richard J. Paulson, Mark V. Sauer. (1994) Regulation of oocyte donation to women over the age of 50: A question of reproductive choice. Journal of Assisted Reproduction and Genetics 11:4, 177-182
CrossRef39
C. T. Fitzgerald, M. W. Seif, S. R. Killick, D. A. Bennett. (1994) Age related changes in the female reproductive cycle. BJOG: An International Journal of Obstetrics and Gynaecology 101:3, 229-233
CrossRef40
MAXINE WEINSTEIN, MARYA STARK. (1994) Behavioral and Biological Determinants of Fecundability. Annals of the New York Academy of Sciences 709:1, 128
CrossRef41
W. Braendle. (1993) Kinderwunsch der Frau über 40. Archives of Gynecology and Obstetrics 254:1-4, 96-102
CrossRef42
PETER T. ELLISON. (1993) Measurements of Salivary Progesterone. Annals of the New York Academy of Sciences 694:1 Saliva as a D, 161-175
CrossRef43
Abraham Benshushan, Joseph G. Schenker. (1993) Age limitation in human reproduction: Is it justified?. Journal of Assisted Reproduction and Genetics 10:5, 321-331
CrossRef44
Jerome H. Check, H. Ali Askari, Jung Choe, Amy Baker, Harriet G. Adelson. (1993) The effect of the age of the recipients on pregnancy rates following donor-oocyte replacement. Journal of Assisted Reproduction and Genetics 10:2, 137-140
CrossRef45
M.V. Sauer, R.J. Paulson, R.A. Lobo. (1993) Pregnancy after age 50: application of oocyte donation to women after natural menopause. The Lancet 341:8841, 321-323
CrossRef46
Gay Becker, Robert D. Nachtigall. (1992) Eager for medicalisation: the social production of infertility as a disease.. Sociology of Health and Illness 14:4, 456-471
CrossRef47
EBRAHIM J. KERMANI. (1992) Issues of Child Custody and Our Moral Values in the Era of New Medical Technology. Journal of the American Academy of Child & Adolescent Psychiatry 31:3, 533-538
CrossRef48
Annas, George J., . (1992) Using Genes to Define Motherhood — The California Solution. New England Journal of Medicine 326:6, 417-420
Full Text49
Maria Zenzes, Robert F. Casper. (1992) Cytogenetics of human oocytes, zygotes, and embryos after in vitro fertilization. Human Genetics 88:4, 367-375
CrossRef50
(1991) New Reproductive Techniques. New England Journal of Medicine 325:14, 1043-1045
Full Text51
S Morcos, M Macnamee, R.G Edwards, D.E Walters, J.P Balmaceda, R Asch. (1991) High fecundity of amenorrhoeic women in embryo-transfer programmes. The Lancet 338:8762, 292-294
CrossRef52
Angell, Marcia, . (1990) New Ways to Get Pregnant. New England Journal of Medicine 323:17, 1200-1202
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