Embryo reduction of multifetal pregnancies following assisted reproduction treatment: a modification of the transvaginal ultrasound-guided technique

First-trimester transvaginal embryo reduction is an effective alternative for the management of multifetal pregnancy in assisted reproduction. We have modified the transvaginal technique by performing an intracardiac embryo puncture until asystolia is verified, without the injection of any substances. Any aspiration of embryo tissues or amniotic fluid was avoided. A total of 149 multifetal pregnancies was reduced to twins (n = 134) or singletons (n = 15) at early gestational age (7.8 +/- 0.8 weeks). Eleven cases (7.3%) of miscarriage, two cases (1.3%) of chorioamnionitis, and 17 cases (11.4%) of transient spotting were recorded as postoperative complications. Vanishing of one embryo occurred in four cases (3.0%) of those reduced to twins. The baby take-home rate was 89.5% for twins and 80.0% for singletons. Pregnancy outcome was analysed and compared with a control group of women with non-reduced multiple pregnancies. The birth weight of singleton pregnancies after reduction was lower (2929 +/- 160 versus 3291 +/- 422 g; P < 0.02). These studies show that early transvaginal intracardiac embryo puncture is an effective and safe technique.     

Factors determining early pregnancy loss in singleton and multiple implantations

BACKGROUND: The incidence of first trimester pregnancy loss is much lower in IVF twin pregnancies than in IVF singleton pregnancies. The objective of this study was to determine which embryonic and maternal factors contribute to this finding. METHODS: Retrospective data analysis of the outcome of 1593 pregnancies after day 3 double-embryo transfer (DET) after IVF or ICSI treatment. RESULTS: Of 1148 single implantations at 6 weeks, 936 (81.5%) were ongoing pregnancies. Of 445 multiple implantations at 6 weeks, 354 (79.6%) were ongoing multiple pregnancies, 80 (17.9%) were ongoing singleton pregnancies and 11 (2.5%) ended in a spontaneous abortion. Total pregnancy loss was 18.5 and 2.5% (P < 0.001) in singleton and twin gestations, respectively. Loss per gestational sac was 18.5 and 11.46% (P < 0.001), respectively. Determinants contributing to the continuation of gestation beyond 6 weeks were young maternal age, possibility to cryopreserve embryos and short GnRH agonist flare-up stimulation protocol. Whereas factors promoting multiple implantation at 6 weeks of gestation were young maternal age, high cumulative embryo score (CES), male infertility, long stimulation protocol and thick endometrium. CONCLUSIONS: Although multiple implantation at 6 weeks is predominantly determined by (morphological) embryo quality, the continuation of pregnancy beyond 6 weeks becomes more dependent on the combination of genetic and developmental potential of the embryo(s) and an optimal uterine milieu.     

Embryo reduction in multifetal pregnancies using saline injection: comparison between the transvaginal and the transabdominal approach.

A total of 30 patients with multifetal pregnancies, all resulting from treatment with superovulatory agents or assisted reproductive techniques, underwent embryo reduction. All patients had three or more fetuses (one sextuplet, two quintuplets, seven quadruplets and 20 triplets). The procedure was carried out using intra-embryonal injection of 0.9% sodium chloride solution. Embryo reduction was carried out via the transabdominal approach in 10 patients, performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other patients, at 8-10 weeks of gestation. In the transabdominal group, one patient aborted following repeated attempts at embryo reduction while the other nine gave birth to healthy newborns (eight twins and one triplet). In the transvaginal group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation), 14 pregnancies resulted in a delivery of at least one live newborn (13 twins and one singleton), one patient had a late abortion at 24 weeks' gestation and another was delivered at 27 weeks' gestation due to severe pre-eclampsia. Transvaginal ultrasound-guided needle procedures are commonly practised in most in-vitro fertilization units. The employment of this route for embryo reduction, performed at an earlier gestational age and with the use of a non-toxic substance such as 0.9% saline solution, is advocated.     

Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody.

Seventeen women with recurrent fetal loss associated with anti-phospholipid antibody were treated by prednisolone and low-dose aspirin (PSL/ASP) therapy from the early gestational period. The success rate of pregnancy in the treated patients was significantly higher than that in 12 untreated patients of similar background, including age, number of previous fetal losses and anti-cardiolipin titre (76.5 versus 8.3%, P less than 0.01). The degree of fetal growth retardation evident in previous pregnancies was also improved by the therapy, suggesting that PSL/ASP itself has a beneficial effect against placental damage. These clinical improvements were accompanied by a reduction in anti-phospholipid antibody titre, especially that of anti-phosphatidylserine antibody (anti-PS), to within the normal range within 8 weeks after PSL/ASP administration in most of the treated patients. There was no reduction of antibody titre in the untreated patients during pregnancy. It was concluded that PSL/ASP therapy, when started in the early gestational period (prior to 8 weeks gestation), was effective for the achievement of successful pregnancy and the prevention of fetal growth retardation and that the anti-PS titre was a good clinical marker for evaluating the effect of PSL/ASP therapy.     

The "vanishing embryo" phenomenon in an oocyte donation programme

BACKGROUND: We studied the incidence of vanishing embryos (VE) in pregnancies achieved by oocyte donation and evaluated the obstetric and perinatal complications. METHOD: A retrospective study was carried out based on a chart review of 399 patients with multiple pregnancies from our oocyte donation programme. We defined vanishing phenomenon as the early resorption, in the first trimester, of one or more embryos in a multiple gestation, after confirming embryonic heart activity by transvaginal ultrasound. RESULTS: Vanishing embryo was observed in 75 patients (18.8%). In 60 patients (80%) this phenomenon occurred before the ninth gestational week. A higher incidence of VE was observed in patients who initially showed a higher number of gestational sacs (P < 0.03). Vaginal bleeding in the first trimester was significantly higher in patients with VE (P < 0.005). Miscarriage rate was similar in pregnancies with and without VE (P = NS). The incidence of pregnancy induced hypertension was decreased in the group with VE (P < 0.03). Preterm spontaneous rupture of membranes occurred more frequently in pregnancies with VE (P < 0.05). However, gestational age at delivery was similar in the group with VE and the controls. CONCLUSIONS: The high incidence of VE in pregnancies achieved by oocyte donation should be considered when counselling patients with high order multiple gestations.     

Heterotopic Caesarean scar pregnancy combined with intrauterine pregnancy successfully treated with embryo aspiration for selective embryo reduction: case report

Ectopic pregnancy situated in a Caesarean section scar is a rare but potentially life-threatening event. Because of its rarity, there are no universal treatment guidelines to manage this condition. We report a case of IVF-induced triplet heterotopic pregnancy of early gestational age that included one Caesarean scar pregnancy diagnosed as early as 6 weeks gestation. Treatment with embryo aspiration under vaginal ultrasonography for selective embryo reduction was given and the concurrent intrauterine twin pregnancy was preserved successfully.     

Obstetric outcome and psychological follow-up of pregnancies after embryo reduction.

The obstetric outcome and psychological follow-up of the parents after embryo reduction performed at Sahlgrenska University Hospital between 1993 and 1997 in 13 women treated for infertility is described. A comparison is made with non-reduced multiple pregnancies, both spontaneous and multiple pregnancies after assisted reproduction technology. Altogether 10 triplets, two quadruplets and one quintuplet pregnancy underwent embryo reduction. The surgical procedure was performed in gestation week 7-8 by transvaginal, ultrasound-guided aspiration of embryonic tissue. The psychological follow-up included personal interviews and psychological evaluations by a Psychological General Well-being Scale (PGWB) and Beck's Depression Inventory (BDI). In 11 cases reduction was performed to twin pregnancies. In two cases of triplets after in-vitro fertilization and transfer of two embryos, reduction was performed on the monozygotic, monochorionic twins. No complete miscarriages occurred. Ten women delivered twins and three women delivered singletons. The mean gestation length was 40.4 weeks for singletons and 35.9 weeks for twins. The mean birthweight was 3411 g for singletons and 2392 g for twins. No complications related to the reduction were detected in the children.The psychological follow-up showed that the psychological well-being of the parents was good. However, the events around the reduction were experienced as chaotic and emotionally disturbing. One woman regretted the reduction. All couples emphasized that avoidance of high order pregnancies should be of primary importance. In conclusion, embryo reduction appears to improve the perinatal outcome of multiple pregnancies obtained after assisted reproduction technology. It is important that the surgical procedure is performed at a centre with experience of this type of intervention, by a limited number of surgeons and in a regulated manner. Psychologically, however, the intervention is traumatic and psychological management is essential for good final outcome.     

The effect of intercourse on pregnancy rates during assisted human reproduction

Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.     

Monozygotic twin delivery following reduction from quadramniotic-dichorionic gestation established after ICSI and embryo transfer: Case report

We report the delivery of healthy monozygous (MZ) twins in a 31 year-old nulligravida following gonadotrophin ovulation induction, ICSI, assisted hatching and fresh embryo transfer. Although a sonogram on day 35 confirmed that two of four transferred embryos had implanted, a second transvaginal sonogram 1 week later showed each gestational sac had two conceptuses-all four were associated with distinct amniotic compartments. Cardiac activity was observed in all four embryos. At 12 weeks and 5 days gestation, chorionic villus sampling was performed on fetuses 1 and 2 which were euploid for chromosomes 13, 18, 21, X and Y via fluorescence in-situ hybridization analysis. Subsequent KCl injection into sacs 3 and 4 resulted in asystole for these fetuses, while cardiac activity in sacs 1 and 2 remained unchanged after reduction. A twin vaginal delivery occurred at 36 weeks gestation, resulting in the birth of two male infants and one placenta. This case represents the first known report of human quadruplet pregnancy consisting of two MZ twin sets conceived by assisted reproductive techniques. Our report reviews proposed mechanisms for explaining twinning, with special emphasis on zona pellucida micromanipulation and subsequent MZ twin induction.     

Preterm delivery and growth restriction in multifetal pregnancies reduced to twins

Gestation at delivery, birthweight and pregnancy outcome of surviving fetuses from 127 multifetal pregnancies undergoing embryo reduction to twins were compared to 354 chromosomally normal non-reduced dichorionic twin pregnancies. First-trimester embryo reduction was carried out by intracardiac injection of KCl. In 16 (12.6%) of the 127 multifetal pregnancies reduced to twins, there was miscarriage of both fetuses before 24 weeks of gestation. The median interval between reduction and fetal loss was 5 weeks (range 1-12). In livebirths, the median gestation at delivery was 36 weeks (range 24-41) and the median difference in birthweight from the appropriate mean was -0.94 SD (range -3.89-1.73 SD). Both fetal loss before 24 weeks and the interval between embryo reduction and delivery were significantly associated with the gestation at reduction (r = 0.40, P < 0.001 and r = -0.57, P < 0.001 respectively). In the pregnancies reduced to twins compared to the non-reduced twins, the percentage of miscarriages was higher (12.6 compared to 2.5%; chi 2 = 19.2, P < 0.001), the median gestation at delivery was lower (36 compared to 37 weeks; t = -1.74, P < 0.05), and the median birthweight deficit was greater (-0.94 compared to -0.65 SD: t = -4.1, P < 0.001).      

经阴道穿刺治疗宫内外同时妊娠4例

目的 探讨经阴道穿刺在宫内外同时妊娠(HP)治疗中的应用及价值.方法 2004年1月至2009年12月广州医学院第三附属医院生殖医学中心体外授精-胚胎移植(IVF-ET)妊娠患者中,筛选出经阴道穿刺治疗的4例HP患者,分析探讨经阴道穿刺治疗HP的适应证、时机的选择、治疗方法及妊娠结局.结果 经阴道穿刺治疗的4例HP均为宫内妊娠合并输卵管妊娠,4例患者宫内妊娠胚胎及异位妊娠胚胎均见原始心管搏动.3例行经阴道穿刺抽吸异位妊娠胚胎,其中2例治疗时间分别为孕42d、43 d,均足月分娩,1例治疗时间为孕68d,穿刺术后4 h输卵管破裂行开腹手术治疗,术后4d宫内妊娠流产.另1例抽吸胚胎后注射50%葡萄糖2 ml,治疗时间为孕50 d,足月分娩.结论 如果HP患者孕周较小(＜8周),病变输卵管未破裂,无明显的腹腔内出血,术后能够有较长时间定期复诊随访,则可以选择经阴道穿刺治疗HP.     

Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review

BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage and early preterm birth. It is uncertain if the outcome is improved by embryo reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER. The two groups were compared for the rates of miscarriage, defined as pregnancy loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition, systematic searches were performed to identify studies comparing outcomes in expectant management versus ER in triplet pregnancies. RESULTS: We combined data from 365 pregnancies managed in our centre with those of five previous studies. In total there were 893 pregnancies. In the ER group (n=482) compared to the expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus 4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036] and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95% CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions needed to be performed to prevent one early preterm delivery, while the number of reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS: In trichorionic triplets, ER to twins is associated with an increase in the risk of subsequent miscarriage and decrease in risk of early preterm birth.     

Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome

BACKGROUND: Frozen embryo transfers are characterized by impaired pregnancy outcome and increased incidence of pregnancy loss as compared with fresh IVF/ICSI embryo transfers. In this study, we performed a retrospective analysis of clinical and embryological factors that potentially influence the outcome of frozen embryo transfer. METHODS: We reviewed the outcome of 1242 frozen embryo transfers with respect to the age of the woman, the method of fertilization, embryo quality before and after freezing and the number of embryos transferred. RESULTS AND CONCLUSIONS: The pregnancy (positive hCG) and clinical pregnancy rates were 25.8 and 21.1%, respectively. A total of 107 (33.3%) of the 321 pregnancies identified by a positive hCG test miscarried either before (18.4%) or after (15%) the clinical recognition of gestational sac(s). The delivery rate for the frozen embryo transfers analysed was 17.2%. Our data revealed that the delivery rate after frozen embryo transfer was dependent on both the woman's age and the quality of embryos transferred, at the same time being unaffected by IVF/ICSI treatment. In addition, the increased woman's age at IVF/ICSI treatment was identified as the only parameter elevating the biochemical pregnancy rate, whereas the clinical abortion rate was found to be unrelated to the clinical or embryological parameters studied.     

Maternal serum HCG is higher in the presence of a female fetus as early as week 3 post-fertilization

BACKGROUND: Maternal serum HCG (MSHCG) is higher when the fetus is a female than when it is male. This has been demonstrated in the second and third trimesters of pregnancy, and recently at 10-14 weeks gestation. In this study we assessed whether this gender-related difference can be detected as early as week 3 post-fertilization. METHODS: The IVF setting was chosen because it provides precise dating of gestational age and early sonography for the number of gestational sacs. The study included 347 IVF cycles from 335 patients. Only pregnancies with a single implanted embryo that resulted in a single live birth of known gender were included. MSHCG was measured on days 14-20 post-fertilization, and levels were expressed as gestational age-corrected multiples of the median (MoMs). The log10 MSHCG MoMs were compared according to fetal gender. RESULTS: MSHCG levels were significantly higher (18.5%) in week 3 post-fertilization in the presence of a female fetus (P < 0.0002). CONCLUSION: Because a fetal gender-related difference in MSHCG can be demonstrated as early as week 3 post-fertilization, the difference may be attributed to placental factors and not to the effects of the fetal hypothalamic-hypophyseal-gonadal axis.     

Consequences of vanishing twins in IVF/ICSI pregnancies

BACKGROUND: Spontaneous reductions are a possible cause of the increased morbidity in IVF singletons. The aim of this study was to assess incidence rates of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and long-term morbidity in survivors of a vanishing co-twin with singletons and born twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237 singletons from single gestations and 3678 twins from twin gestations. All children originated from pregnancies detected by transvaginal sonography in gestational week 8. By cross-linkage with the national registries the main endpoints were prematurity, birth weight, neurological sequelae and mortality. RESULTS: Of all IVF singletons born, 10.4% originated from a twin gestation in early pregnancy. Multiple logistic regression analyses adjusted for maternal age, parity and ICSI treatment showed for birth weight <2500 g an odds ratio (OR) of 1.7 [95% confidence interval (CI) 1.2-2.2] and for birth weight <1500 g OR 2.1 (95% CI 1.3-3.6) in singleton survivors of a vanishing twin versus singletons from single gestations; corresponding figures were seen for preterm birth. This increased risk was almost entirely due to reductions that occurred at >8 weeks gestation. We found no excess risk of neurological sequelae in survivors of a vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was 1.9 (95% CI 0.7-5.2). Furthermore, we observed a correlation between onset of spontaneous reduction, i.e. the later in pregnancy the higher the risk of neurological sequelae (r = -0.09; P = 0.02). Adjusted OR of child death within the follow-up period was 3.6 (95% CI 1.7-7.6) in the survivor versus the singleton cohort. CONCLUSIONS: One in 10 IVF singletons originates from a twin gestation. Spontaneous reductions that occur at >8 weeks gestation are one of the causes for the higher risk of adverse obstetric outcome in IVF singletons.     

Development of the secondary human yolk sac: correlation of sonographic and anatomical features.

Transvaginal ultrasound examination of the secondary yolk sac was performed in 145 first trimester pregnancies with a normal outcome (Group A), in 10 normal pregnancies undergoing artificial termination (Group B) and in 25 pregnancies that subsequently failed (Group C) due to embryonic death (n = 17) or to spontaneous abortion of a live embryo (n = 8). The yolk sac structure of all cases from Group B and from 12 cases of Group C were examined morphologically, in order to investigate the changes secondary to normal yolk sac senescence or to pregnancy complication and to evaluate the relationship existing between these changes and ultrasound features. The yolk sac diameter measured in vivo increased significantly between 6 and 10 weeks of gestation and then decreased significantly. Morphologically, the yolk sac showed degenerative changes after 9 weeks of gestation suggesting that the disappearance of the yolk sac in normal pregnancies was a spontaneous event of embryonic development rather than the result of mechanical compression by the expanding amniotic cavity. Yolk sac measurements in complicated pregnancies were not predictive of pregnancy outcome. Irrespective of gestational age, important degenerative changes were found in pregnancies complicated by embryonic death or disappearance, suggesting that variation of yolk sac size and appearance in these cases is the consequence of abnormal embryonic development of death rather than being the primary cause of early pregnancy failure.     

Human zona pellucida micromanipulation and monozygotic twinning frequency after IVF

To assess the association of zona pellucida micromanipulation and subsequent development of monozygotic twins, cases of assisted embryo hatching (AH) and intracytoplasmic sperm injection (ICSI) were identified and related to treatment type, implantation and zygosity data. Embryology records from all patients undergoing in-vitro fertilization (IVF) at this centre from January 1995 to March 1998 were reviewed. In this study, 3546 transfer cycles were completed, with clinical pregnancy established in 1911 (54% per transfer) patients undergoing a single IVF cycle. These pregnancies occurred in 1674 (88%) IVF cycles, 120 (6%) donor oocyte cycles (DER), and 117 (6%) frozen embryo transfer (FET) cycles. During the study period, 23 cases of monozygotic (MZ) twins were identified, representing an overall frequency of 1.2%. Chorionicity was determined by transvaginal ultrasound at 7 weeks when the number of embryos transferred was less than the number of fetal heart-beats, or when >1 fetal heartbeat per gestational sac was seen. Zygosity was confirmed by placental evaluation at delivery, and corroborated the antenatal diagnosis in all cases. Among IVF study patients the frequency of MZ twinning was not statistically different between zona manipulated and zona intact subgroups. While this investigation is the largest to date describing the relationship between MZ twins and zona procedures, studies with even greater statistical power are needed to clarify it more precisely, particularly in DER and FET settings. A greater overall frequency of MZ twinning for IVF patients may be a function of the higher number of embryos transferred in IVF, rather than discrete zona manipulations.     

Is intracytoplasmic sperm injection (ICSI) a safe procedure? What do we learn from early pregnancy data about ICSI?

The aim of this study was to evaluate the safety of the intracytoplasmicsperm injection (ICSI) procedure by analysing early pregnancydata from ICSI and in-vitro fertilization (IVF) patients. Inall, 50 ICSI pregnancies were compared with 226 FVF pregnancies.Comparisons were made during the first 9 weeks after the theoreticallast menstrual period (7 weeks after oocyte retrieval) withregard to epidemiological data, plasma hormonal concentrationsand transvaginal ultrasonographical findings. Although patientswere significantly (P < 0.001) younger in ICSI (31 years)than in IVF pregnancies (33 years), their duration of infertilitywas similar. Miscarriage and multiple gestation rates were notsignificantly different in ICSI pregnancies (respectively 24and 24%) from those found after IVF (32 and 29%). The probabilityof developmental arrest of the intrauterine sac (miscarriagesand vanishing twins) was similar in both ICSI (16%) and IVF(25%) cases. The mean plasma hormonal concentrations startingfrom day 11 after oocyte retrieval were similar in both groups.Every ICSI and IVF pregnancy showed an embryo with cardiac activityat 7 weeks. Early pregnancy data did not show any abnormal findingsfor pregnancies achieved using ICSI compared to those achievedby FVF.     

Elective single embryo transfer: the value of cryopreservation

In-vitro fertilization is associated with a high rate of multiple pregnancies, a consequence of the number of embryos transferred. There is a challenge in avoiding even twin pregnancies in assisted reproduction, and this can be accomplished with elective single embryo transfer and a good cryopreservation programme. In our follow-up study, we analysed all our elective single embryo transfers during 1998-1999. In all these cycles at least one embryo was frozen. A total of 127 elective single embryo transfers were performed with a clinical pregnancy rate of 38.6%. The highest implantation rate was obtained with four-cell embryos with <10% fragmentation (39.8%). Thirty-four patients have delivered (26.8%), one of these being a monozygotic pregnancy. In total 129 frozen-thawed cycles have been achieved in 83 patients. One frozen-thawed embryo has been transferred in 46 cycles with a clinical pregnancy rate of 17.4%, and two embryos have been transferred in 83 cycles, with a clinical pregnancy rate of 37.3%. Up until now, 66 of 125 patients in our single embryo transfer programme have delivered or have on-going pregnancies, and 77 still have embryos frozen. The cumulative delivery rate per oocyte retrieval is 52.8% and the twin rate 7.6%. We conclude that elective single embryo transfer with a good cryopreservation programme results in very acceptable pregnancy rates with a low risk of twins. This is a cost-effective practice that substantially reduces all risks associated with multiple pregnancies and lowers the cost per delivery.     

Survival rates during the first trimester of multiple gestations achieved by ICSI: a report of 1448 consecutive multiples

BACKGROUND: The purpose of this study was to determine the rate of spontaneous gestational sac loss during the first trimester in women achieving multiple pregnancies by ICSI. METHODS: A retrospective analysis was performed of 1448 consecutive multiple pregnancies conceived by ICSI. RESULTS: Of the cohort of 1448 pregnancies, twin gestations constituted 59.6% (864), triplets 30.2% (438) and quadruplets 10.0% (146). During the first trimester, 69 (4.7%) patients miscarried, while 179 (12.3%) continued their pregnancies and had fewer gestational sacs at the end of the first trimester than at the beginning. The overall loss rate of any gestational sac during the first trimester in these multiple pregnancies was 10.1%. There was a significant difference in the frequency of spontaneous reduction to twin or singleton pregnancies in the first trimester between women carrying triplets (11.7%) and those carrying quadruplets (3.5%) [P = 0.004; odds ratio (OR) 3.5; 95% confidence interval (CI) 1.3-9.1]. The frequency of gestational sac loss was significantly greater among women >35 years old (20.9%) than in women less than 35 years old (15.9%) (P = 0.03; OR 1.4; 95% CI 1.0-1.9). CONCLUSION: In multiple pregnancies there is a significant risk of spontaneous loss of any embryo during the first trimester. These findings should be considered prior to any decision about selective embryo reduction.