Early IVF Pregnancy Research Articles

β-hCG elevation rate in early IVF pregnancies and obstetrical complications

IVF pregnancies are associated with higher prevalence of placental complications such as hypertensive disorders of pregnancy and growth restriction. Abnormal β-hCG elevation is strongly associated with short-term adverse pregnancy outcomes such as miscarriage and ectopic pregnancies. However, the significance of slow β-hCG elevation rate on pregnancies that do continue to live birth is unknown. Single center retrospective cohort study between 2008-2019 including 818 fresh cycles resulting in a live singleton birth. The study was approved by the institutional ethics committee. The first blood β-hCG measurement was performed 15±1 days after oocyte pickup and the second 2.2±0.6 days later. The slope between the two measurements was calculated and adjusted per two days. Slow hCG elevation was defined as a slope value below the 10th percentile (< 1.766). Maternal and neonatal outcomes were compared between cycles with a slow elevation (n=82) and a “normal” elevation (n=736) in hCG values. Multivariate analysis was used to control for potential confounders. There were no differences between the groups in baseline maternal and IVF treatment characteristics (Table 1). Newborns from cycles with a slow β-hCG elevation weighed significantly less (2913±626 gr vs. 3081±549 gr, p< 0.01). There was no significant difference in the rate of small for gestational age newborns. Women with a slow β-hCG elevation had significantly more gestational hypertension (10% vs 4%, OR 3.50, 95% CI 1.50-8.11) and preeclampsia related disorders (11% vs 3%, OR 3.51, 95% CI 1.58-7.80). This association remained significant after correcting for potential confounders (including maternal age, gestational age at delivery and nulliparity), in a multivariate analysis. There was no difference in preterm labor rates as well as mode of delivery between the groups (Table 2). Early pregnancy (4th-5th week) β-hCG elevation rate might be a novel marker for identifying patients at risk for hypertensive obstetrical complications. Tighter prenatal care could potentially reduce adverse pregnancy outcome.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

P-770 Is there an association between blood hCG elevation rate in very early IVF pregnancy and adverse pregnancy outcomes?

Abstract Study question Is a slow elevation rate between the first and second hCG values following a successful fresh IVF cycle associated with long-term pregnancy outcomes? Summary answer A slow rate of hCG elevation in early IVF pregnancies is associated with an increased risk for low birth weight neonates. What is known already IVF pregnancies are associated with higher prevalence of late obstetrical complications such as preterm birth, preeclampsia and small for gestational age. Different baseline characteristics and treatment parameters are associated with obstetrical complications. Abnormal, mostly slow, hCG elevation patterns have been strongly associated with short-term adverse pregnancy outcomes such as non-viability, miscarriage, early fetal demise and ectopic pregnancies. However, the long-term impact of slow hCG elevation rate on pregnancies that do continue to term is unknown. Study design, size, duration Single center cohort study between 2008-2019 including 703 fresh cycles resulting in live singleton birth. Full obstetrical data for these pregnancies was available. Participants/materials, setting, methods The first blood hCG measurement was performed 14±1.4 days after ovum pick-up (OPU), and the second one 48-72h later. The slope between the two measurements was calculated and adjusted per day. Slow hCG elevation was defined as a slope value below the 10th percentile. Maternal and short-term neonatal outcomes were compared between cycles with a slow elevation (n = 71) and a “normal” elevation (n = 632) in hCG values. Multivariate analysis was used to control for potential confounders. Main results and the role of chance There were no differences between the slow and normal hCG elevation groups in maternal age, numbers of retrieved oocytes, ICSI rates, number of transferred and usable embryos, and gestational age at delivery. Neonates from cycles with a slow hCG elevation weighed significantly less (2876±619 gr vs. 3083±553 gr, p &amp;lt; 0.005) and were at a higher risk (21% vs. 12%, OR = 1.96, 95% CI 1.06-3.64) of having low birth weight (LBW) (below 2500 grams). Women with slow hCG elevation rate had more hypertension-preeclampsia related complications (11% vs. 6%, p &amp;lt; 0.05), although barely reaching statistical significance in the multivariate analysis (OR = 1.76, 95% CI 1.0-3.6). Limitations, reasons for caution Retrospective design, single center, applicability to fresh cycles only. Wider implications of the findings Very early (5th week) initial blood hCG elevation slope, measured only in IVF gestations, might be a novel marker for identifying patients at risk for hypertensive complications during pregnancy and low birth-weight neonates. Tighter prenatal care for these patients could potentially reduce pregnancy complications and improve long-term outcome. Trial registration number not applicable

DO EARLY HCG DYNAMICS AFTER EMBRYO TRANSFER DIFFER BASED ON DAY OF EMBRYO BIOPSY?

Serum HCG threshold levels and rate of rise are established predictors of successful pregnancy in IVF embryo transfer cycles. While prior studies on HCG dynamics in early IVF pregnancies have accounted for factors such as stage of embryo development, these studies have not accounted for the speed of embryo development. Day 7 embryos have been shown to have reduced implantation potential.1 However, no study has yet to review the relationship between day 7 embryo transfer and the level of HCG secretion when early pregnancy is achieved. The objective of this study is to compare initial HCG levels and the rate of HCG increase between day 5, 6, and 7 single, euploid frozen embryo transfers (FET). The study included patients who underwent a single, euploid FET, from January 2012 to March 2021. Initial serum HCG levels were reviewed on day 9 post FET, and if positive, the rate of HCG rise, by day 11, was noted. FET cycles were stratified by day of embryo biopsy and cryopreservation (Group A: Day 5; Group B: Day 6; Group C: Day 7). Baseline demographics were compared and analyzed by ANOVA and Kruskal-Wallis. A logistic regression was then performed to evaluate the differences in HCG levels when controlling for Patient Age, Oocyte age, BMI, AMH, BAFC, day 3 FSH, and endometrial thickness at progesterone initiation. A total of 1,707 single euploid FETs were included and separated into three groups: Group A (n = 1,104), Group B (n = 577), and Group C (n = 26). The mean serum HCG value on day 9 after ET was 168.7 in Group A, 143.0 in Group B, and 94.8 in Group C. Initial HCG level and the percent of HCG rise was significantly different between the three groups (p < 0.0001). Day 5 embryos had a significantly higher absolute difference in HCG levels, from day 9 to day 11, compared with day 6 embryos (OR 1.41 [95% CI 1.23-1.75]) and day 7 embryos (OR 4.74 [95% CI 2.16-10.40]). The percent rise of HCG between days 9 and 11 in day 5 embryos was significantly lower than day 7 embryos (OR 2.36 [95% CI 1.079-5.16]), but was similar compared with day 6 embryos (OR 1.19 [95% CI 0.955-1.48]). The HCG dynamics of early pregnancies from a single, euploid FET, are significantly impacted by the day of embryo development. Our findings show that reproductively competent day 7 embryos have lower initial HCG levels, but then a higher rate of HCG rise compared with faster growing day 5/6 embryos. The increased rate of HCG rise in day 7 embryos may reflect a mechanism such as compensation for a delayed activation of the embryonic transcriptome which these slower growing embryos are able to overcome to be able to successfully implant.

Conception after early IVF pregnancy loss: should we wait?

Research questionIs the interval length between an early pregnancy loss and the following treatment cycle a predictor for achieving clinical pregnancy among IVF patients? DesignThis retrospective cohort study of 257 women who reinitiated treatment after first-trimester IVF pregnancy loss was conducted at a tertiary, university-affiliated medical centre between 1 January 2014 to 1 January 2018. Women aged 18–40 years, with normal uterine cavity, who experienced first-trimester pregnancy loss at less than 14 weeks after IVF, were included. Miscarriages were classified as spontaneous, biochemical, medical or surgical. ResultsAmong 257 women, interval to subsequent IVF treatment was not associated with achieving pregnancy. Patients after biochemical pregnancy (72.7 ± 56.4, median 60 days) or spontaneous miscarriage (97.7 ± 93.1, median 66 days) had shorter intervals to next cycle, compared with medical (111.9 ± 103.2, median 65 days) or surgical (123.4 ± 111.1, median 84 days) (Kaplan–Meier, P = 0.03) miscarriages.Logistic regression analysis showed that the chance of subsequent pregnancy was affected by the number of embryos transferred (P = 0.009) and the type of miscarriage. Medical (P = 0.005) and surgical (P = 0.017) miscarriages were related to lower likelihood of pregnancy compared with biochemical pregnancy (reference group).When pregnancy was achieved in the first post-miscarriage cycle, the chance of live birth increased with shorter intervals (median 57.5 days), whereas second miscarriage was related to longer intervals (median 82.5 days) between miscarriage and subsequent IVF cycle (P = 0.03). ConclusionOn the basis of this cohort, IVF should not be postponed after pregnancy loss, as shorter intervals were associated with greater likelihood of live birth.

Maternal β-HCG concentrations in early IVF pregnancy: association with the embryo development stage of blastocysts.

Does the blastocyst development stage on embryo transfer day affect serum β-human chorionic gonadotrophin (β-HCG) concentration 9 and 16 days after embryo transfer in women whose pregnancy progresses beyond 13 weeks? Retrospective study involving 204 cases where pregnancy progressed beyond 13 weeks of single blastocyst transfer in fresh (n=66) or frozen embryo transfer (FET) (n=138) cycles from January 2015 to September 2016. β-HCG concentrations 9 and 16 days after embryo transfer in FET cycles (median 223IU/l and 4378IU/l, respectively) were significantly (P<0.001) higher than in fresh cycles (157IU/l and 2813IU/l). Among fresh cycles, faster-growing blastocysts (expanded + hatching + hatched blastocysts) produced significantly (P<0.001) higher β-HCG concentrations 9 days after embryo transfer (191IU/l) than slower-growing blastocysts (cavitating + full blastocyst, 106IU/l); however no significant difference was found between the faster- and slower-growing groups by day 16 (2359IU/l and 3025IU/l, respectively). Among FET cycles, there was no difference in β-HCG concentration between blastocysts of different development stages 9 and 16 days after transfer. Faster-growing blastocysts produced significantly higher serum β-HCG concentrations 9 days after transfer than slower-growing blastocysts in fresh cycles, but the difference was not significant by day 16 after transfer. Also, β-HCG concentrations 9 and 16 days after embryo transfer in FET cycles were higher than in fresh embryo transfer cycles. Interpretation of β-HCG results 9 days after blastocyst transfer should consider the blastocyst growth rate and whether fresh or cryopreserved embryo was transferred.

Low risk of venous thromboembolism following early pregnancy loss in pregnancies conceived by IVF

What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF? The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF. There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks). A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included. We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies. During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies. Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions. The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors. No external funding was obtained for this study. There are no conflicts of interest to declare.

Maternal concentrations of human chorionic gonadotrophin in very early IVF pregnancies and duration of pregnancy: a follow-up study.

Are maternal concentrations of human chorionic gonadotropin (HCG) on a fixed day after embryo transfer associated with duration of pregnancy? A follow-up study of 1917 singleton pregnancies after IVF was performed. Embryos were cultured for 2 days and maternal HCG concentration quantified on day 12 after embryo transfer. Duration of pregnancy was obtained from the Medical Birth Registry of Norway. Association of HCG concentration (log2-transformed) with duration of pregnancy was estimated as hazard ratios (HR) with 95% confidence intervals (CI) by applying Cox regression proportional hazard models, where time to delivery for pregnancies shortened because of planned Caesarean delivery or induction of labour was treated as censored. The estimated median duration of pregnancy from embryo transfer was 266 days (95% CI 266-267 days). Maternal concentration of HCG on day 12 after embryo transfer varied from 1 to 588 IU/l (median 117 IU/l). Duration of pregnancy decreased by increasing HCG concentration, significantly in pregnancies delivered at full term ((257-270 days after embryo transfer; HR 1.127, 95% CI 1.026-1.238, P = 0.012). For each doubling of HCG concentration on day 12 after embryo transfer, duration of pregnancy was shortened by 0.51 days. Adjustment for maternal age, prepregnancy body mass index, being a first-time mother and number of embryos transferred did not change the association. High maternal HCG concentration on a fixed day after embryo transfer is likely to indicate early embryo implantation. After embryo transfer, pregnancies with early implantation are shorter than pregnancies with late implantation.

Maternal hCG concentrations in early IVF pregnancies: associations with number of cells in the Day 2 embryo and oocytes retrieved.

Do number of cells in the transferred cleavage stage embryo and number of oocytes retrieved for IVF influence maternal hCG concentrations in early pregnancies? Compared with transfer of a 2-cell embryo, transfer of a 4-cell embryo results in higher hCG concentrations on Day 12 after transfer, and more than 20 oocytes retrieved were associated with low hCG concentrations. Maternal hCG concentration in very early pregnancy varies considerably among women, but is likely to be an indicator of time since implantation of the embryo into the endometrium, in addition to number and function of trophoblast cells. We followed 1047 pregnancies after IVF/ICSI from oocyte retrieval until Day 12 after embryo transfer. Women were recruited in Norway during the years 2005-2013. Successful pregnancies after transfer of one single embryo that had been cultured for 2 days were included. Maternal hCG was quantified on Day 12 after embryo transfer by chemiluminescence immunoassay, which measures intact hCG and the free β-hCG chain. Information on a successful pregnancy, defined as birth after >16 weeks, was obtained by linkage to the Medical Birth Registry of Norway. Transfer of a 4-cell embryo resulted in higher maternal hCG concentrations compared with transfer of a 2-cell embryo (134.8 versus 87.8 IU/l, P < 0.05). A high number of oocytes retrieved (>20) was associated with low hCG concentrations (P < 0.05). The factors studied explain a limited part of the total variation of hCG concentrations in early pregnancy. Although embryo transfer was performed at the same time after fertilization, we do not know the exact time of implantation. A further limitation to our study is that the number of pregnancies after transfer of a 2-cell embryo was small (27 cases). Number of cells in the transferred embryo and number of oocytes retrieved may influence the conditions and timing for embryo implantation in different ways and thereby influence maternal hCG concentrations. Such knowledge may be important for interpretation of hCG concentrations in early pregnancy.

The role of magnesium and thyroid function in early pregnancy after in-vitro fertilization (IVF): New aspects in endocrine physiology

BackgroundThe initiation of a pregnancy is a process that requires adequate energetic support. Recent observations at our Institution suggest a central role of magnesium in this situation. The aim of this study was to evaluate magnesium, zinc, selenium and thyroid function as well as anti-Müllerian hormone in early pregnancy following in-vitro fertilization as compared to spontaneous successful pregnancies. ResultsA successful outcome of pregnancy after IVF treatment was associated with 2 parameters: higher levels of anti-Müllerian hormone as well as higher levels of magnesium in the pre-stimulation blood sample. These two parameters, however, showed no correlation. Spontaneous pregnancies as well as pregnancies after IVF show a fall of magnesium levels at 2–3 weeks of gestation. This drop of magnesium concentration is larger following IVF as compared to spontaneous pregnancies. Parallel to these changes TSH levels showed an increase in early IVF-pregnancy. At this time point we also observed a positive correlation between fT4 and TSH. This was not observed in spontaneous pregnancies. Thyroid antibodies showed no correlation to outcomes. ConclusionsIn connection with the initiation of pregnancy following ovarian stimulation dynamic changes of magnesium and TSH levels can be observed. A positive correlation was found between fT4 and TSH in IVF pregnancies. In spontaneous pregnancies smaller increases of TSH levels are related to higher magnesium levels. General significanceWe propose that magnesium plays a role in early pregnancy as well as in pregnancy success independently from anti-Müllerian hormone. Neither thyroid hormones nor thyroid antibodies were related to outcome.

Interleukin-2 and SOCS-1 proteins involvement in the pathophysiology of severe ovarian hyperstimulation syndrome--a preliminary proof of concept.

BackgroundOvarian hyperstimulation syndrome (OHSS), is characterized by marked ovarian enlargement and acute third space fluid sequestration that almost always develops after hCG administration or in early pregnancy. OHSS is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines. In the present pilot exploratory case series, we sought to evaluate interleukin (IL)-2 and suppressor of cytokine signaling (SOCS)-1 expressions in the peripheral blood mononuclear cells (PBMCs) of patients suffering from severe ovarian hypertimulation syndrome (OHSS), and to examine whether their expressions differ when compared to PBMCs originated from normal early pregnant women (without OHSS).MethodsInterleukin-2 and SOCS-1 mRNA expressions were examined in PBMCs of 5 women who were hospitalized due to severe OHSS (OHSS group) and 5 women with early IVF pregnancies and without OHSS (control group).ResultsInterleukin-2 mRNA levels in PBMCs were significantly higher in the OHSS as compared to the control groups. Moreover, while SOCS-1 mRNA levels were non-significantly lower, the ratio between IL-2 and SOCS-1 mRNA levels was significantly higher in the OHSS, as compared to the control group.ConclusionsThe inflammatory response to hCG, leading to dysregulation of Il-2 expression and SOCS activation, might be the culprit of OHSS. Additional large prospective studies are required to elucidate the effect of hCG on patients’ inherited inflammatory cascades, which may help discriminating those at risk to develop severe OHSS from those who are not.

Maternal serum ghrelin levels in early IVF pregnancies: lack of prognostic value for viable pregnancy and altered post-prandial responses

Ghrelin is a pleiotropic hormone, involved in the control of growth and metabolism, whose circulating levels fluctuate in relation to food intake and body mass index. Ghrelin has been detected in the decidualized endometrium, as well as in human and rat placenta. A total of 106 patients undergoing IVF procedures were prospectively recruited. On Days 16 and 23 after oocyte retrieval, the patients were subjected to blood sampling after overnight fasting, for determination of serum ghrelin, hCGbeta and progesterone levels. In addition, ghrelin levels were assayed in these groups, 2 h after ingestion of a fixed-calorie meal. The subjects were divided according to whether they achieved an ongoing pregnancy. On Days 16 and 23 after oocyte retrieval, pre-prandial serum ghrelin levels were not statistically different, although a general trend toward a decrease in circulating ghrelin by Day 23 was detected in pregnant groups. Although in non-conceiving subjects, maternal ghrelin levels showed an expected 15% decline after meal ingestion, such a post-prandial decrease was not statistically significant in pregnant women, selectively on Day 16 after oocyte retrieval. Maternal ghrelin levels at early gestational age do not appear to pose diagnostic (as marker) or prognostic value for pregnancy outcome in IVF procedures.

Low endometrial volume may predict early pregnancy loss in women undergoing in vitro fertilization

To evaluate the role of 3-D US measurement of the endometrium during early IVF-pregnancy and before the appearance of gestational sac in the prediction of pregnancies outcome. 60 pregnant women following IVF treatment were included in the study. The women underwent transvaginal 3D US measurements of endometrial volume and thickness on day 15-17 post ET. Patients were followed and classified according to pregnancy outcome into 2 further groups. The group with early pregnancy loss and the group with ongoing pregnancy. While no differences were observed between those who miscarried and those who did not in gestational age, endometrial thickness or volume, spontaneous early pregnancy loss was significantly higher in patients with endometrial volume <2 mL as compared to those with endometrial volume >2 mL. 3-D US measurement of endometrial volume of less than 2 mL during early IVF pregnancy and prior to the appearance of gestational sac is a powerful predictor of pregnancy loss.

P-531: Lack of prognostic value of maternal serum ghrelin levels in early IVF pregnancies for gestational outcome and altered post-prandial responses

Ghrelin is a pleiotropic hormone recently involved in the control of growth and metabolism, whose circulating levels fluctuate in relation to food intake and body mass index. Elevated RNA-Ghrelin levels in the decidualized endometrium have been reported and it is present in the human and rat placenta showing a pregnancy related time course expression. The aim of this study is to evaluate the clinical value of maternal Ghrelin serum measurements at very early stages of IVF pregnancies. In addition, ghrelin responses to food intake were explored at early gestation. Prospective study. One hundred and seven patients who underwent embryo transfer were prospectively recruited. On d-16 and 23 after oocyte retrieval, the patients were subjected to blood sampling after overnight fasting, for determination of serum ghrelin, hCGβ and progesterone levels. In addition, ghrelin levels were assayed in these groups, 2-h after ingestion of a fixed-calorie meal. The subjects were divided into the following groups: women that failed to conceive (non-pregnant; n=36), women who had a viable intra-uterine pregnancy (on-going pregnancy), either singleton (n=28) or twin (n=24), and abnormal pregnancies: biochemical (n=9) and miscarriage (n=7). There was no significant difference in patient′s age, number of oocytes retrieved, and embryos transferred during the IVF cycles among groups. On 16th and 23 th day, the mean plasma ghrelin concentration after an overnight fasting were similar among the different groups. Interestingly, while in non-pregnant subjects maternal ghrelin levels showed an expected ∼15% decline after meal ingestion, such a post-prandial decrease was not detected in pregnant women, selectively at d-16 after oocyte retrieval (p < 0.05). Maternal ghrelin levels at early gestational age do not appear to pose diagnostic (as marker) or prognostic value for pregnancy outcome in IVF procedures. The lack of decline in serum ghrelin levels in response to meal ingestion reported herein is likely to be a novel component of the extensive metabolic adaptations that take place at early pregnancy. Longer series and at different pregnancy weeks are needed to better address this issue.

Gamma-Interferon and IL-2 receptor levels predict the outcome of IVF pregnancies

Gamma-Interferon and IL-2 receptor levels predict the outcome of IVF pregnancies

Heterotopic pregnancy complicating in vitro fertilization.

A review was undertaken of the cases of heterotopic pregnancy resulting from in vitro fertilization/embryo transfer (IVF/ET) and frozen embryo replacement (FER) in a 6-year cohort of women at National Women's Hospital in Auckland. The incidence of heterotopic pregnancy was 2.9% (5 cases) in 173 clinical pregnancies resulting from 901 embryo replacements. Of the 5 women with heterotopic pregnancy, 1 had unilateral tubal patency and 4 had bilateral tubal blockage; 3 had 'high responder' peak serum oestradiol levels (greater than 9,000 pmol/L) prior to oocyte pick-up (OPU); 3 had a serum human chorionic gonadotrophin beta subunit (beta-HCG) level greater than 600 IU/L on Day 14 following embryo transfer (ET) in the absence of a multiple intrauterine gestation on subsequent ultrasound scan. In the 4 women in whom unequivocal diagnosis of heterotopic pregnancy was not made on the initial ultrasound scan, there was delay in appropriate management, in 1 for more than 5 months. In conclusion, early IVF pregnancies require a transvaginal ultrasound scan performed by a sonographer experienced in the diagnosis of ectopic pregnancy and management of early pregnancy complications by clinicians in close consultation with the IVF centre itself. No single risk factor, laboratory test or combination of these is sensitive or specific enough to predict the occurrence of heterotopic pregnancy. The first-line surgical treatment of heterotopic pregnancy should be laparoscopic salpingectomy with excision of all except the intramural portion of the affected Fallopian tube.