1 Departments of Obstetrics and Gynecology, The Lis Maternity Hospital, 6 Weizman St, Tel Aviv 46427, 2 The Sheba Medical Center, Tel-Hashomer and 3 Wolfson hospital, Holon and The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel
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Abstract |
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Key words: first and second trimester bleeding/gestational diabetes mellitus/hypertensive disorders in pregnancy/oocyte donation/perinatal outcome
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Introduction |
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Oocyte donation patients represent a unique parturient population because of the high incidence of advanced maternal age, often >45 years, and the high proportion of women with dysfunctional ovaries.
Most of the previous studies that have assessed the obstetric outcome after oocyte donation reported high rates of complications, such as pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM) and first trimester bleeding (FTB). However, these studies were based on a small number of women or were limited to only few obstetric or perinatal outcome measures (Serhal and Craft, 1989; Blanchette, 1993
; Pados et al., 1994
; Sauer et al., 1995
, 1996
; Remohi et al., 1997
; Abdalla et al., 1998
; Söderström-Anttila et al., 1998
; Yaron et al., 1998
). Moreover, very limited information is available regarding the risk factors affecting the perinatal outcome of these pregnancies.
The purpose of this study was to determine the obstetric and perinatal outcome of 134 singleton pregnancies following oocyte donation and to evaluate the interaction of these outcome variables with selected risk factors.
Patients and methods
We enrolled 170 consecutive women who conceived following oocyte donation at the Assuta IVF Unit in Tel-Aviv and who delivered between January 1995 and February 1999. In order to eliminate the confounding variable of multiple pregnancies, typically associated with a higher rate of obstetric and perinatal complications, we elected to restrict our study group to the 134 gestations with a singleton fetus. The steroid replacement regimen used was determined according to the preference of the individual attending.
Obstetric and perinatal data were collected in all cases through review of medical files and by detailed post-partum questionnaires and personal interviews. In particular, we recorded the maternal age (advanced maternal age was defined as an age at delivery >45 years), parity, smoking during pregnancy, previous uterine scar, extent of ovarian function at conception, PIH [classified according to the American College of Obstetrics and Gynecology criteria (ACOG technical bulletin, 1996)], GDM, FTB and second trimester bleeding (STB). Outcome variables included preterm delivery (PD) (delivery at <37 gestational weeks), low birth weight (LBW; <2500 g), small for gestational age [SGA, defined as a birth weight lower than the fifth percentile using the intrauterine curves of Alexander (Alexander et al., 1996
)], Caesarean delivery, and need for admission to the neonatal intensive care unit (NICU).
Congenital malformations were classified according to Myrianthopoulos and Chung. (Myrianthopoulos and Chung, 1974).
Statistical analyses
Results are reported as mean ± SD, or n (%). Multiple stepwise logistic regression analysis was used to evaluate the association between a specific discrete perinatal outcome variable and the above mentioned demographic or obstetric variables. Odds ratios (ORs) and their 95% confidence interval (CI) were calculated. P < 0.05 was considered significant.
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Results |
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The incidence of PIH was 27.6%. The women were further classified as having chronic hypertension (2.2%), gestational hypertension (10.4%), pre-eclampsia (5.2%) or severe pre-eclampsia (6.7%); 2.9% could not be classified. The rate of hypertension among women >45 years was 30%, non-significantly different from the 22% rate in women <45 years. The rates of GDM, FTB and STB were 23.9, 43.3 and 6% respectively. Among the women who developed GDM, 28.1% required insulin for adequate glycaemic control. Approximately 20% of the women had a spontaneous vaginal delivery. While 72% of the women had Caesarean deliveries, more than half of them were non-elective.
The mean ± SD length of gestation was 38.0 ± 2.6 weeks. The rate of PD, LBW and SGA were 14.9, 14.9 and 7.6% respectively. The mean birth weight was 2998 g. There were no cases of perinatal mortality, and the rate of major congenital malformations was 2.2%.
Table I depicts the ORs and 95% CIs for the factors associated with PD, LBW, babies born SGA, deliveries by Caesarean section and the need for NICU. PD was significantly associated with PIH, STB and maternal smoking. LBW deliveries were significantly associated with PIH, STB, nulliparity and maternal smoking. The delivery of an SGA baby was significantly associated with PIH. A stay in the NICU was significantly associated with GDM, STB and maternal smoking. These adverse perinatal outcomes were not significantly associated with advanced maternal age (>45 years) or ovarian failure. Caesarean delivery was associated with advanced maternal age, PIH, GDM and a previous uterine scar.
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Discussion |
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FTB was the most frequently observed obstetric complication, presenting in 43.3% of our patients. Vaginal bleeding was reported to occur very frequently (1215%) after oocyte donation (Pados et al., 1994; Abdalla et al., 1998
; Söderström-Anttila et al., 1998
). It has been suggested that FTB may be linked to early resorption of one or more fetuses in pregnancies that were multifetal early on (Shaw and Sauer, 1995
). However, this seems unlikely in oocyte donation pregnancies since, first, transfer of only two oocytes per cycle has been reported to result in a high frequency (53%) of FTB (Söderström-Anttila et al., 1998
) and second, IVF pregnancies (without oocyte donation) are associated with a low percentage of FTB (Tan et al., 1992
; Söderström-Anttila et al., 1998
). Another theoretical explanation is that the steroid replacement therapy received by the patient does not always provide the best endocrine environment for embryonic development. The aetiology for the high rate of FTB is yet to be explained. Nevertheless, the influence on pregnancy outcome seems limited and FTB was not associated with adverse perinatal effects.
In our series, there was no difference in the frequency of FTB between patients with ovarian failure and those with functioning ovaries; this finding is consistent with that of Söderström-Anttila et al. (Söderström-Anttila et al., 1998), but differs from the results reported by Pados et al (Pados et al., 1994
).
The high rate of STB was unexpected since it has not been previously reported. Other authors reported rates of 5.8% (Pados et al., 1994) and 1% (Abdalla et al., 1998
). In the series of Lipitz et al. in spontaneous pregnancies, STB was present in only 1% of the women, and was associated with a fetal loss of 32% (Lipitz et al., 1991
). It is known that STB, even of short duration, is associated with adverse fetal outcome (Yang and Savitz, 2001
). In our series, STB was significantly associated with PD and LBW deliveries, and with an increased length of stay in the NICU.
The rate of chronic hypertension among our parturients was only 2.2%. However, hypertensive disorders in pregnancy were the second most frequently observed obstetric complication in our patients. This is consistent with previous reports showing rates varying between 23 and 38% (Serhal and Craft, 1989; Blanchette, 1993
; Pados et al., 1994
; Sauer et al., 1995
, 1996
; Abdalla et al., 1998
; Söderström-Anttila et al., 1998
; Yaron et al., 1998
). This is in contrast with an incidence of PIH of 612% in the general population (Sibai et al., 1993
; Gifford et al., 2000). It has been suggested that the increased rate of hypertension in oocyte donation pregnancies is related to advanced maternal age, nulliparity and ovarian failure (Pados et al., 1994
; Yaron et al., 1998
; ACOG practice bulletin, 2002
). However, in our study, these were not independent risk factors for hypertensive disorders in pregnancy, which is consistent with others findings (Abdalla et al., 1998
; Söderström-Anttila et al., 1998
). Despite the multifactorial pathophysiology of PIH, more recent reports provide further support to the hypothesis that the development of PIH in oocyte recipients may be due to altered or inadequate immunoprotection of the feto-placental unit, due to the short duration of exposure to non-maternal antigens (Salha et al., 1999
; Wang et al., 2002
). The evidence that pre-eclampsia may be a disorder of the immunological mechanism involved in the normal feto-maternal host response includes several mechanisms, which indicate that exposure to paternal antigens is protective. In the oocyte recipient, immunological hyporesponsiveness can be explained either by an increased likelihood of human leukocyte antigen sharing between the mother and the two sets of paternal and donor oocyte histocompatibility antigens, or by an excessive antigenic load overwhelming the responder state, features that are more prominent in patients with ovarian failure. However, an article by Hall et al. does not support this theory, as, in their study which compared IVF pregnancies with donor sperm and with partner sperm, it was shown that long-term sexual cohabitation offers no protection from hypertensive disease of pregnancy (Hall et al. 2001
). Nevertheless, hypertensive disorders in pregnancy were strongly associated with perinatal complications, such as PD, LBW and SGA deliveries. All of the complications noted above are well known to occur in hypertensive disorders in pregnancy regardless of its context (Cunningham et al., 2001
; Ray et al., 2001
).
GDM was seen in 23.9% of the women in this study, while the incidence of GDM in the general population is reported to be 2.5% (Xiong et al., 2001). Many diabetic women in our study (28.6%) required insulin for adequate glycaemic control. Advanced maternal age was not associated with a higher rate of GDM. Diabetes in pregnancy was associated with an increased rate of Caesarean deliveries and a greater rate of admissions to the NICU. The latter can probably be explained by the fact that infants born to a diabetic mother are more likely to be admitted to the NICU for blood sugar monitoring.
In spite of the high motivation of women who conceive through oocyte donation, in our series 13.4% of them smoked throughout pregnancy. As expected, smoking was associated with increased PD and LBW deliveries, and subsequently with more frequent stays in the NICU (Stillman et al., 1986; Voight et al., 1990
).
Nulliparity was associated with LBW deliveries, which may be due to the fact that, in general, nulliparous women deliver children of lower birth weight than multiparous women (Seidman et al., 1988).
The rate of Caesarean deliveries was exceptionally high (72.3%), consistent with previous reports (Blanchette, 1993; Pados et al., 1994
; Sauer et al., 1996
; Abdalla et al., 1998
; Söderström-Anttila et al., 1998
; Yaron et al., 1998
). The performance of the procedure was affected by the presence of PIH and GDM, advanced maternal age, and a previous uterine scar. All of the above-mentioned conditions are known risk factors for Caesarean delivery, but oocyte donation may represent an additional, independent risk factor (Dulitzki et al., 1998
).
In terms of perinatal outcome variables, it may appear that the rate of PD was not strikingly elevated, at 14.9%. This actually might not be entirely true, since in Israel, the rate of premature deliveries is much lower than in the USA, at 7% (Melamed et al., 2000
). Moreover, the rate of 7% in Israel is an overall one, including both singleton and multiple pregnancies, while this study, including only singleton pregnancies, should have led to an even lower rate than that in the general population. This would suggest that the rate of PD is high in singleton oocyte donation pregnancies, which is consistent with the recent finding that infants conceived with use of assisted reproduction technology, including IVF, are associated with a similarly high rate of prematurity even in singleton pregnancies (Bergh et al., 1999
; Scheive et al., 2002
).
Encouragingly, the rate of major congenital malformations was similar to that observed in the general population, which is in contrast with the recent finding that infants conceived with the use of IVF have twice as high a risk of congenital malformations as naturally conceived infants (Hansen et al., 2002). However, the power to detect any difference compared with the general population is very low in our study, due to the limited number of patients included.
A limitation of the present study is the lack of a control group. However, an appropriate control group would be difficult, if not impossible, to obtain because it would require the selection of spontaneously pregnant women at similar ages. An unbiased match is unlikely as fertility strikingly decreases with advancing age. Nevertheless, our study provides important risk estimates which should be made available to women electing to undergo oocyte donation.
In summary, our study, among the largest series of its type, revealed a high risk of obstetric complications in singleton oocyte donation pregnancies. Patients should be counselled about these risks prior to undergoing oocyte donation, and should be carefully monitored for these complications during pregnancy. Nevertheless, in spite of these obstetric complications, it appears from our study that the perinatal outcome is overall favourable.
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Notes |
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References |
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ACOG technical bulletin (1996) Hypertension in pregnancy. Number 219 January 1996.
ACOG practice bulletin (2002) Clinical Management Guidelines for ObstetricianGynecologists. Obstet. Gynecol., 99, 159167.
Alexander, G.R., Himes, J.H., Kaufman, R.B., Mor, J. and Kogan, M. (1996) A United States national reference for fetal growth. Obstet. Gynecol., 87, 163168.
Bergh, T., Ericson, A., Hillensjo, T., Nygren, K.-G. and Wennerholm, U.-B. (1999) Deliveries and children born after in-vitro fertilization in Sweden 198295: a retrospective cohort study. Lancet, 453, 15791585.
Blanchette, M.D. (1993) Obstetric performance of patients after oocyte donation. Am. J. Obstet. Gynecol., 168, 18031809.[ISI][Medline]
Cunningham, F.G., Gant, N.F., Leveno, K.J., Gilstrap, L.C., Hauth, J.C. and Wenstrom, K.D. (2001) Hypertensive disorders in pregnancy. In Williams Obstetrics, 21nd edn, McGraw-Hill, USA, pp. 567618.
Dulitzki, M., Soriano, D., Schiff, E., Chetrit, A., Mashiach, S. and Seidman, D.S. (1998) Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery. Obstet. Gynecol., 92, 935939.
Gifford, R.W., August, P.A., Cunningham, G., Green, L.A., Lindheimer, M.D., McNellis, D., Roberts, J.M., Roccella, E.J., Sibai, B.M. and Taler, S.J. (2002) Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am. J. Obstet. Gynecol., 183, S1S22.
Hall, G., Noble, W., Lindow, S. and Masson, E. (2001) Long term sexual co-habitation offers no protection from hypertensive disease of pregnancy. Hum. Reprod., 16, 349352.
Hansen, M., Kurinczuk, J.J., Bower, C. and Webb, S. (2002) The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N. Engl. J. Med., 346, 725732.
Lipitz, S., Admon, D., Menczer, J., Ben-Baruch, G. and Oelsner, G. (1991) Midtrimester bleeding: Variables which affect the outcome of pregnancy. Gynecol. Obstet. Invest., 32, 2427.[ISI][Medline]
Melamed, Y., Bashiri, A., Shoham-Vardi, I., Furman, B., Hackmon-Ram, R. and Mazor, M. (2000) Differences in preterm delivery rates and outcomes in Jews and Beduins in Southern Israel. Eur. J. Obstet. Gynecol. Reprod. Biol., 93, 4146.[ISI][Medline]
Myrianthopoulos, N.C. and Chung, C.S. (1974) Congenital malformations in singletons: epidemiology survey: report from the collaborative perinatal project. Birth Defects Orig. Artic Ser., 10, 158.
Pados, G., Camus, M., Van Steirteghem, A., Bonduelle, M. and Devroey, P. (1994) The evolution and outcome of pregnancies from oocyte donation. Hum. Reprod., 9, 538542.[Abstract]
Ray, J.G., Burrows, R.F., Burrows, E.A. and Vermeulen, M.J. (2001) MOS HIP: McMaster outcome study of hypertension in pregnancy. Early Hum. Dev., 64, 129143.[ISI][Medline]
Remohi, J., Gartner, B., Gallardo, E., Yalil, S., Smon, C. and Pellicer, A. (1997) Pregnancy and birth rate after oocyte donation. Fertil. Steril., 64, 717723.
Salha, O., Sharma, V., Data, T., Nugent, D., Rutherford, A.J., Tomlinson, A.J., Philips, S., Allgar, V. and Walker, J.J. (1999) The influence of donated gametes on the incidence of hypertensive disorders of pregnancy. Hum. Reprod., 14, 22682273.
Sauer, M.V., Paulson, R.J. and Lobo, R.A. (1995) Pregnancy in women 50 or more years of age: outcomes of 22 consecutively established pregnancies from oocyte donation. Fertil. Steril., 64, 111115.[ISI][Medline]
Sauer, M.V., Paulson, R.J. and Lobo, R.A. (1996) Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older. Hum. Reprod., 11, 25402543.[Abstract]
Scheive, L.A., Meikle, S.F., Ferre, C., Peterson, H.B., Jeng, G. and Wilcox, L.S. (2002) Low and very low birth weight in infants conceived with use of assisted reproductive technology. N. Engl. J. Med., 346, 731739.
Seidman, D.S., Ever-Hadani, P., Stevenson, D.K., Slater, P.E., Harlap, S. and Gale, R. (1988) Birth order and birth weight reexamined. Obstet. Gynecol., 72, 158162.[Abstract]
Serhal, P.F. and Craft, I.L. (1989) Oocyte donation in 61 patients. Lancet, i, 11851187.
Shaw, K.J. and Sauer, M.V. (1995) Obstetric care of surrogates and recipients of donor oocytes. Semin. Reprod. Endocrinol., 13, 237243.[ISI]
Sibai, B.M., Caritis, S.N., Thom, E., Klebanoff, M., McNellis, D., Rocco, L.R.N., Paul, R.H., Romero, R., Witter, F., Rosen, M. et al. and the National Institute of Child Health and Human Development Network of MaternalFetal Medicine Unit (1993) Prevention of preeclampsia with low dose aspirin in healthy, nulliparous pregnant women. N. Engl. J. Med., 329, 12131218.
Society for Assisted Reproductive Technologies, American Society for Reproductive Medicine (2002) Assisted reproductive technology in the United States and Canada: 1998 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil. Steril., 77, 1831.[ISI][Medline]
Söderström-Anttila, V., Tiitinen, A., Foudila, T. and Hovatta, O. (1998) Obstetric and perinatal outcome after oocyte donation: comparison with in-vitro fertilization pregnancies. Hum. Reprod., 13, 483490.[ISI][Medline]
Stillman, R.J., Rosenberg, M.J. and Sachs, B.P. (1986) Smoking and reproduction. Fertil. Steril., 46, 545566.[ISI][Medline]
Tan, S.L., Doyle, P., Campbell, S., Beral, V., Rizk, B., Brinsden, P. and Mason, E.R.G. (1992) Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies. Am. J. Obstet. Gynaecol., 167, 778784.[ISI][Medline]
Voight, L.F., Hollenbach, K.A., Krohn, M.A., Daling, J.R. and Hickok, D.E. (1990) The relationship of abruptio placentae with maternal smoking and small for gestational age infants. Obstet. Gynecol., 75, 771774.[Abstract]
Wang, J.X., Knottnerus, A.M., Schuit, G., Norman, R.J., Chan, A. and Dekker G.A. (2002) Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet, 359, 673674.[ISI][Medline]
Xiong, X., Saunders, L.D., Wang, F.L. and Demianczuk, N.N. (2001) Gestational diabetes mellitus: prevalence, risk factors, maternal and infant outcomes. Int. J. Gynaecol. Obstet., 75, 221228.[ISI][Medline]
Yang, J. and Savitz, D.A. (2001) The effect of vaginal bleeding during pregnancy on preterm and small for gestational age birth: US National Maternal and Infant Health Survey, 1988. Paediatr. Perinat. Epidemiol., 15, 3439.[ISI][Medline]
Yaron, Y., Ochshorn, Y., Amit, A., Kogosowski, A., Yovel, I. and Lessing, J.B. (1998) Oocyte donation in Israel: a study of 1001 initiated treatment cycles. Hum. Reprod., 13, 18191824.[Abstract]
Submitted on April 2, 2002; accepted on July 11, 2002.