The ISMAAR proposal on terminology for ovarian stimulation for IVF

IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient-centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients.     

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.     

Sigmoid endometriosis and ovarian stimulation

In-vitro fertilization (IVF) and ovarian stimulation are frequently performed in patients with endometriosis. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low. We report four cases of severe digestive complications due to the rapid growth of sigmoid endometriosis under ovarian stimulation. In three patients, sigmoid endometriosis was diagnosed at laparoscopy for sterility. Because of the absence of digestive symptoms or repercussion on the bowel, no bowel resection was performed before ovarian stimulation. All patients experienced severe digestive symptoms during ovarian stimulation, and a segmental sigmoid resection had to be performed. Analysis of endoscopic and radiological data demonstrated that bowel lesions of small size may rapidly enlarge and become highly symptomatic under ovarian stimulation. At immunohistochemistry, these infiltrating lesions displayed high populations of steroid receptors and a high proliferative index (Ki-67 activity), suggesting a strong dependence on circulating ovarian hormones and a potential for rapid growth under supraphysiological oestrogen concentrations. Clinicians should be aware of this rare but severe digestive complication of ovarian stimulation. The early diagnosis of such lesions may help the patients to avoid months of morbidity falsely attributed to ovarian stimulation side effects. Further experience is necessary to determine the optimal attitude when diagnosing a small and asymptomatic endometriotic bowel lesion before ovarian stimulation.     

Internal jugular vein thrombosis after ovarian stimulation

Thromboembolic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. Here, we report a case of internal jugular vein thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or hereditary hypercoagulability. Screening for these risk factors in our patient was negative. The patient was successfully treated with low molecular weight heparin and a twin pregnancy is ongoing.     

Predictors of low response to mild ovarian stimulation initiated on cycle day 5 for IVF

BACKGROUND: Milder stimulation protocols are being developed to minimize adverse effects of ovarian stimulation in in vitro fertilization (IVF) programs. A drawback is the possibility of an increased rate of insufficient ovarian response. This study aimed to develop a prognostic model for the prediction of cycle cancellation due to insufficient response to mild stimulation. METHODS: A total of 174 IVF patients aged<38 years and with a body mass index (BMI)<28 Kg/m2 were treated with mild ovarian stimulation using a fixed daily dose (150 IU) of recombinant follicle-stimulating hormone (rFSH) from cycle day 5 and GnRH antagonist from the late follicular phase. In women with mono- or bifollicular growth (17%), the cycle was cancelled and the treatment was adjusted in a second treatment cycle by starting rFSH on cycle day 2. RESULTS: In a multivariable logistic regression analysis, duration of infertility, menstrual cycle length, secondary infertility and BMI were included in the prediction model. The area under the receiver-operating characteristics curve of the model was 0.69. A probability cut-off for cancellation of 0.3 yielded an expected sensitivity of 33% and specificity of 92%. Analysis of ovarian response in the subsequent treatment cycle showed an improved ovarian response and a significant reduction in the cancellation rate. CONCLUSIONS: With the presented model, it is possible to identify patients at risk for cycle cancellation, during mild ovarian stimulation, due to insufficient response. The contributing factors of the model suggest that ovarian aging and BMI are related to insufficient response to mild stimulation.     

Efficacy of natural cycle IVF: a review of the literature

Since the introduction of IVF treatments, natural cycle IVF has been largely replaced by IVF with ovarian stimulation. However, natural cycle IVF has several advantages. It is associated with a close to zero multiple pregnancy rate, and a zero risk of ovarian hyperstimulation syndrome. Per cycle, natural cycle IVF is less time consuming, physically and emotionally less demanding for patients, and cheaper than stimulated IVF, but also less effective. This systematic literature review addresses the issue of effectiveness of natural cycle IVF. Herein, 20 studies describing natural cycle IVF are presented; 12 case series and eight in which a comparison was made between natural cycle IVF and IVF with ovarian stimulation. Good-quality randomized controlled trials and formal cost-effectiveness analyses are lacking. The 20 selected studies comprised a total of 1800 cycles of natural cycle IVF, resulting in 819 embryo transfers (45.5% per cycle) and 129 ongoing pregnancies (7.2% per cycle and 15.8% per embryo transfer). Efficacy of natural cycle IVF is hampered by high cancellation rates because of premature LH rise and premature ovulations. It is concluded that natural cycle IVF is a low-risk, low-cost and patient-friendly procedure. A randomized controlled trial comparing natural cycle IVF with current standard treatment strategies is warranted.     

Perinatal outcome and developmental studies on children born after IVF

Since the first birth after IVF, many scientific papers have been published on the technical aspects of the IVF procedure, but few studies have addressed the issue of the perinatal outcome of IVF pregnancies and of the children's development and well-being. A high rate of adverse outcome has been demonstrated in a large group of IVF pregnancies. Prematurity, low birth weight and perinatal mortality are higher than in the general population. The majority of these complications are related to multiple births, but they are also found in singleton pregnancies. An analysis of the multiple risk factors involved in these complications is needed. The infertile status of IVF patients clearly plays a role in the risk of adverse outcome. Age and parity may be important factors. The role of IVF itself has not been demonstrated convincingly. The effect of ovarian stimulation deserves further study. Most of the studies published on the follow-up of IVF children are reassuring, but it is clear that these studies are not sufficient to eliminate without doubt any adverse effects on the well-being of IVF children. All IVF pregnancies should be followed with great care, not because they are more precious than spontaneous pregnancies, but because they are exposed to an increased risk of complications. The main problem of IVF remains the high rate of multiple pregnancies, including twins.     

Infertility: Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome

Improvements in oocyte culture technique, sperm preparation,oocyte retrieval method and ovarian stimulation regimens haveproduced higher pregnancy rates with in-vitro fertilization(IVF) treatment. However, because ovarian stimulation is expensiveand not without risk, there is increasing interest in the optionof using natural cycles for IVF. This study was performed todocument the experience and outcome in 240 natural cycles. Cancellationoccurred in 28 cycles (12%), and LH surge was observed in 56(23%), leaving 156 (65%) cycles which progressed to oocyte retrieval.No oocytes were retrieved in 26 cycles. Among the successfuloocyte retrievals, the majority yielded one oocyte. There wasno evidence of fertilization in 26 cases, and triploid fertilizationwas observed in 12 cases. Embryos suitable for transfer wereavailable in 92 cycles in which 11 (12%) clinical pregnancieswere confirmed. Despite the high failure rate at each step inthe process, natural cycles are more cost-effective than stimulatedcycles which incur an incremental cost per live birth of $48000. Natural cycles offer a low-cost alternative that may bemore accessible to patients.     

Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures.

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovarian stimulation. In severe cases, haemoconcentration, hypovolaemia, thromboembolism and death may result. It is reassuring that its incidence is not increased after ovarian stimulation for in-vitro fertilization despite very high serum oestradiol levels and large numbers of follicles and oocytes. This may be related to follicular aspiration, expert monitoring or low implantation rates. However, complete prevention has not been achieved despite the wide availability of ultrasound and oestradiol assays, thus presenting the clinician with a continuous challenge. Our aim is to analyse critically the most recent published series of OHSS in in-vitro fertilization and other assisted reproduction techniques using stimulation with gonadotrophin releasing hormone agonists (GnRHa) and human menopausal gonadotrophin (HMG). The main determining factor in the development of OHSS appears to be ovarian predisposition. Patients with polycystic ovarian disease are at a high risk of OHSS and therefore a small dose and slow start of HMG is recommended, tailoring the dosage according to the ovarian response. Accurate prediction by ultrasound and oestradiol assays and strict prevention by withholding human chorionic gonadotrophin (HCG) or cryopreservation of all the embryos have a major impact on the occurrence of OHSS. It is interesting that fixed-schedule IVF cycles, without detailed monitoring, are not associated with an increased incidence of OHSS. The use of GnRHa, despite expectations, is associated with a higher prevalence of OHSS. Luteal phase supplementation with progesterone rather than HCG should be used in cycles where oestradiol is greater than 2500 ng/l or where the number of oocytes exceeded 10.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylactic salpingectomy does not impair the ovarian response in IVF treatment

To examine the effect of prophylactic salpingectomy in patients with hydrosalpinges on the ovarian response to stimulation prior to IVF, 26 patients were included in a study in which they acted as their own controls. They were all part of a randomized controlled study, in which they had been randomized to no surgical intervention prior to IVF. After one or two failed cycles, they underwent laparoscopic uni- or bilateral salpingectomy of their diseased tubes. The cycles before and after surgery were compared and the ovarian response was assessed as the dose and duration of gonadotrophins and the number of retrieved and fertilized oocytes. There were no significant differences in any of the measured outcomes. The increasing age between cycles did not influence the ovarian response, assessed by a comparison with two matched control groups from the same original study; 46 patients salpingectomized before IVF and 25 patients without surgery. It is concluded that removal of hydrosalpinx as a prophylactic laparoscopic procedure does not compromise ovarian function.     

Decreased ovarian reserve relates to pre-eclampsia in IVF/ICSI pregnancies

BACKGROUND: Pre-eclampsia affects 2-10% of all pregnancies and is a major cause of maternal and fetal morbidity and mortality. As compared with the general population, IVF pregnancies are associated with a 2.7-fold risk of pre-eclampsia. An advanced age and associated subfertility in the IVF group reflects a general decrease in ovarian reserve, which itself has been linked to cardiovascular disease. We tested the hypothesis that decreased ovarian reserve is associated with pre-eclampsia as a vascular complication in IVF/ICSI pregnancies. METHODS: In this retrospective case-control study, 41 cases with a history of pre-eclampsia were compared to 82 matched controls without hypertension or (pre)eclampsia. All pregnancies were established after IVF or ICSI. Several indicators of ovarian reserve such as variables related to basal ovarian function and response to hyperstimulation were compared in both the groups by multivariate analysis. The condition of the neonates was evaluated as well. RESULTS: A higher amount of total administered FSH and FSH per day, together with a lower number of obtained oocytes during IVF treatment, were associated with an increased risk to pre-eclampsia in a subsequent pregnancy. The administered FSH per follicle and per obtained oocyte showed even stronger relationships, the latter having the best predictive value. Neonatal outcome was comparable between the groups. CONCLUSION: Diminished responsiveness of the ovaries to FSH stimulation in an IVF cycle, reflecting decreased ovarian reserve, is associated with an increased risk of developing pre-eclampsia in a subsequent pregnancy.     

Thromboembolism after ovarian stimulation: successful management of a woman with superior sagittal sinus thrombosis after IVF and embryo transfer: case report

The current literature was reviewed in order to analyse the clinical manifestations, progression and management, and pregnancy outcome of thromboembolism in infertile patients undergoing ovarian stimulation. The first case of superior sagittal sinus thrombosis following IVF that was successfully managed with intracranial thrombectomy is also reported. This retrospective cohort study comprised 65 women who experienced thromboembolism after ovarian stimulation (64 from other published studies and the present case report). Thrombosis attack occurred at a mean (+/-SD) of 25.5 +/- 20.1 days after oocyte retrieval. The onset timing in the intracranial thrombosis group (10.2 +/- 4.6 days) was less (P < 0.05) than in those experiencing thromboembolism at other sites. Ovarian hyperstimulation syndrome (OHSS), haemoconcentration and high serum estradiol level were noted in 79, 62 and 54% of women respectively. Forty-eight of 55 patients (87%) who received anticoagulation recovered without sequelae. Among patients willing to continue pregnancy, 32% succeeded in term delivery with all healthy babies, and 23% were ongoing pregnancies. In conclusion, ovarian stimulation cycles accompanying high serum estradiol levels, haemoconcentration or OHSS are at potential risk of thromboembolism. Dose-adjusted heparinization is recommended as the first-line treatment of choice, while intravascular thrombolysis or operative thrombectomy is an aggressive but effective treatment. Continuation of pregnancy is considered safe, without any increased risk of fetal congenital anomalies.     

Evaluation of the utility of multiple endocrine and ultrasound measures of ovarian reserve in the prediction of cycle cancellation in a high-risk IVF population

BACKGROUND: Unexpectedly poor response leading to IVF cycle cancellation is a distressing treatment outcome. We have prospectively assessed several markers of ovarian reserve in a high risk IVF population to determine their utility in predicting IVF cycle cancellation. METHODS: Eighty-four women at high risk of cycle cancellation due to raised FSH, previous poor response and/or age > or =40 years attending for high-dose short protocol IVF treatment had baseline measures of FSH, inhibin B, anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume. A GnRH agonist was then administered and, 24 h later, estradiol (E(2)) and inhibin B measures were repeated. RESULTS: Fifty-seven per cent of patients in this study had a poor response to stimulation, and 15% were cancelled. Using multivariate logistic regression, we found that day 3 inhibin B levels were the best predictor of cycle cancellation with an area under the receiver operating curve (ROC AUC) = 0.78 (P = 0.017). When only considering baseline variables, mean ovarian volume was the best predictor of cycle cancellation (ROC AUC = 0.78; P = 0.016). AMH concentrations were the best predictor of a poor response (P = 0.003), and AMH was also predictive of cycle cancellation (P = 0.007) with very little inter-cycle variability. None of the parameters studied were predictive of ongoing pregnancy. CONCLUSIONS: This group of at-risk patients had a high rate of poor response to simulation and cancellation. Although several measures of ovarian reserve were able to predict cycle cancellation, none were able to predict pregnancy. AMH was predictive of both cycle cancellation and poor response with little inter-cycle variability.     

Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint

BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.     

When to avoid creating surplus human embryos

The advice that should be given to a couple considering assisted reproductive technologies for the treatment of their infertility, when they are completely opposed to the destruction of surplus embryos, is discussed. It is urged that they do not use treatments that generate surplus embryos. They should be given the options of declining IVF and considering adoption, or less efficient treatments, namely limited ovarian stimulation, limited insemination of available ova or natural cycle IVF where no surplus embryos are generated.     

Addition of GnRH antagonist in cycles of poor responders undergoing IVF

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.     

Cumulative pregnancy rates after three cycles of minimal stimulation IVF and results according to subfertility diagnosis: a multicentre cohort study

BACKGROUND: In minimal stimulation IVF, treatment is aimed at using the single oocyte that spontaneously develops to dominance. To prevent untimely ovulation, a GnRH antagonist is administered in the late follicular phase of the natural cycle together with recombinant FSH for substitution. Owing to the lack of ovarian stimulation, minimal stimulation IVF is a low-risk and patient-friendly treatment. In this study, effectiveness of minimal stimulation IVF was studied. METHODS: In this prospective multicentre cohort study, minimal stimulation IVF was offered to 350 patients. All indications for conventional IVF were included. Main outcome measures were pregnancy rates per cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 336 patients completed 844 cycles (2.5 per patient). The overall ongoing pregnancy rate per started cycle was 8.3% [95% confidence interval (CI) 6.4-10.2%]. The cumulative ongoing pregnancy rate after up to three cycles was 20.8% (95% CI 16.4-25.3%) per patient. No differences were found according to indication for IVF. CONCLUSIONS: Minimal stimulation IVF seems suitable for all indications studied. Pregnancy rates are encouraging. Owing to the low-risk and patient-friendly nature of this protocol, it seems a feasible treatment option for patients requiring IVF.     

Studies on the influence of gonadotrophin levels in the early follicular phase on the ovarian response to stimulation

The gonadotrophic regulation of folliculogenesis has been extensively investigated but little attention has been paid to the influence of early follicular phase levels of endogenous FSH and the FSH/LH ratio when planning ovulation stimulation therapy for IVF. The influence of these factors was investigated in the three studies reported in this paper. A fixed schedule of ovulation stimulation therapy which employed standard treatment regimens, irrespective of the ovarian response, was used to eliminate variation due to treatment factors. Cycles were pretreated with an oestrogen-progestogen contraceptive pill or a progestogen (norethisterone). It was found that both oestrogen-progestogen and progestogen alone decreased the plasma FSH level, although the FSH/LH ratio was significantly reduced only by oestrogen-progestogens. In clinical IVF studies, oestrogen-progestogen pretreatment was associated with a significant reduction in the preovulatory concentration of oestradiol in plasma and the number of aspirated follicles, compared to norethisterone. The administration of FSH for 2 days following oestrogen-progestogen pretreatment and prior to the fixed schedule of ovulation stimulation normalized ovarian steroidogenesis and follicular development. Early follicular phase supplementation with FSH had no influence on progestogen pretreated cycles. The final experiment investigated the influence of FSH/LH levels in the early follicular phase on the outcome of ovarian stimulation. The preovulatory oestradiol concentration was reduced when baseline FSH/LH levels were low compared with when these values were high. Administration of FSH for 2 days in the early follicular phase improved the preovulatory level of oestradiol when baseline FSH/LH was low but had no effect when baseline FSH/LH levels were high.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blastocyst development and pregnancies after IVF of mature oocytes retrieved from unstimulated patients with PCOS after in-vivo HCG priming.

A major side-effect of controlled ovarian stimulation (COS) in patients with polycystic ovarian syndrome (PCOS) is the risk of ovarian hyperstimulation syndrome (OHSS). In-vitro maturation (IVM) of immature oocytes represents a potential alternative for the fertility treatment of these patients. Two patients at high risk of OHSS were primed with 10,000 IU HCG 36 h before oocyte retrieval. After retrieval, oocyte maturity was evaluated. Oocytes considered to be mature at the time of collection were inseminated by IVF or ICSI, and the resulting embryos were cultured to blastocysts. Transfer of these blastocysts resulted in pregnancy in both patients. Immature oocytes were cultured in YS medium supplemented with 30% human follicular fluid, 1 IU/ml rFSH, 10 IU/ml HCG and 10 ng/ml epidermal growth factor (rhEGF). After in-vitro maturation of the oocytes, ICSI was performed. Two and five expanded blastocysts were obtained after 5 day culture and were cryopreserved. This report indicates that mature oocytes can be collected at the time of retrieval using only in-vivo HCG priming in women with PCOS, and clinical pregnancy can be established by transfer of blastocysts derived from the mature oocytes. This approach opens a potential for a new dimension in the management of patients with PCOS.     

Quantitative assessment of subendometrial blood flow by three-dimensional-ultrasound is an important predictive factor of implantation in an in-vitro fertilization programme

This study was designed to investigate the role of three-dimensional (3D) power Doppler sonography of the (sub-) endometrial area on the first day of ovarian stimulation in predicting the outcome of an in-vitro fertilization (IVF) programme. Among the 75 cycles analysed, the overall pregnancy rate was 20% (15/75) per cycle and 23.8% (15/63) per embryo transfer. Intra-observer variability of the colour histogram was checked in 14 patients with the results demonstrating a high level of agreement. Neither endometrial measurements nor uterine blood flow were correlated with the pregnancy rate. In contrast, all 3D indices were significantly lower in conception compared with non-conception cycles (P < 0.05). Logistic regression analysis found the subendometrial flow index to be the strongest predictive factor of IVF success among the tested sonographic parameters (P = 0.04). In conclusion, quantitative assessment of spiral artery blood flow may be of predictive value for implantation in IVF cycles even before ovarian stimulation therapy is started.