What do women undergoing in vitro fertilization (IVF) understand about their chance of IVF success?

STUDY QUESTION: How well informed are Australian women who undergo IVF about their chances of having a baby? SUMMARY ANSWER: Only one in four women estimated their individual chance of success with IVF accurately, with most women overestimating their chance. WHAT IS KNOWN ALREADY: Limited knowledge about infertility and infertility treatment in the general population is well-documented. The few studies that have investigated patients' knowledge about the chance of IVF success suggest that while IVF patients are aware of average success rates, they tend to be unrealistic about their own chance of success. STUDY DESIGN, SIZE, DURATION: We conducted an anonymous online survey of 217 women who had started IVF since 2018 in Australia. The survey was advertised on social media, enabling women from across Australia to participate. Responses were collected in June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey included questions on demographic characteristics and IVF history. It asked what participants thought their chance of having a baby from one IVF treatment cycle was, how they rated their knowledge about chance of success, and about their experience of receiving IVF-related information. Participants' estimations of their chance of success were compared with their chance as calculated by the Society for Assisted Reproductive Technology's (SART) online calculator. Responses to a free-text question about what information women wished they had been given when they started treatment were analysed thematically. MAIN RESULTS AND THE ROLE OF CHANCE: Only about a quarter (58/217, 27%) of participants accurately estimated their chance of having a baby within 20% relative to their SART calculated chance, with more than half (118/217, 54%) overestimating their chance. Ninety percent of women indicated that their preferred source of treatment information was a consultation with their doctor, despite less than half (44%) reporting that doctors explained the probability of having a baby with IVF well (mean 5.9/10). In free-text responses, many women also reported that they wished they had been given more realistic information about IVF and their chance of success. LIMITATIONS, REASONS FOR CAUTION: The dissemination method precludes calculation of response rate, and it is not possible to know if participants are representative of all women undergoing IVF. Additionally, we only surveyed women undergoing IVF, while those who decided not to have IVF were not included. Therefore, women who overestimated their chance may have been overrepresented. There is also inherent imprecision in the way understanding of chance of success was estimated. The potential impact of recall bias could neither be quantified nor excluded. It is difficult to determine to what extent women's lack of understanding of what is possible with IVF is due to poor information-provision by clinicians and the clinic, and how much can be explained by optimism bias. WIDER IMPLICATIONS OF THE FINDINGS: The finding of poor understanding of personal chance of success amongst women undergoing IVF in Australia requires further investigation to determine potential reasons for this. The findings can be used by clinics to develop strategies for improvement in the information-provision process to ensure that women can make informed decisions about their fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This study received no external funding. S.L. is supported by a NHMRC Investigator Grant (APP1195189). R.W. is supported by a NHMRC Investigator Grant (APP2009767). B.W.M. is supported by a NHMRC Investigator Grant (GNT1176437). B.W.M. reports consultancy for Merck and ObsEva and has received research funding and travel funding from Merck. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Differences between the pre-menopausal and post-menopausal uterine fibroid vasculature.

OBJECTIVES: To quantitatively examine differences in microvascular density between fibroid and myometrial tissue from fibroid uteri removed at hysterectomy, both before and after the menopause, and with hormone replacement therapy. METHODS: Factor VIII immunostaining of formalin fixed tissues was used to identify blood vessels, and the vessels counted by an investigator blinded to tissue type or menopausal status. RESULTS: The mean myometrial: fibroid MVD ratio was 2.38 higher in the post-menopausal group (95% CI: 0.12, 4.65, p=0.0474) than in the pre-menopausal group, with the hormone therapy (HT)-using post-menopausal group lying in between. An increase in microvascular density in the myometrium after the menopause was responsible for most of the change in ratios seen between the pre and post-menopausal pairs. There was a trend to increasing myometrial MVD with increasing number of years post-menopause. CONCLUSIONS: Myometrial microvascular density increases markedly after the menopause, while fibroid microvascular density does not alter. Thus, the difference between myometrial and fibroid vasculature becomes greater after the menopause. The implications of this for the treatment of fibroids in post-menopausal women is discussed.

An immunohistochemical analysis of fibroid vasculature.

This study aimed to compare vascular parameters between fibroid and myometrium. From 10 uteri, specimens were taken from small fibroids (<0.5 cm), from the inner and outer parts of large fibroids (>3 cm), and from myometrium. Antibodies to endothelial cell markers CD31, CD34, factor VIII-related antigen (FVIII), and Ulex europaeus lectin were used in routine immuno- and lectin chemistry protocols. Parameters calculated were vascular area (VA), microvascular density (MD) and vascular luminal diameter. VA measures showed that myometrium had a greater area stained than small fibroids (P = 0.03) using CD31 and both inner (P = 0.04) and outer (P = 0.01) regions of large fibroids using FVIII, and than all groups (small, P = 0.02; inner, P = 0.02; outer, P = 0.006) using the lectin U. europaeus. MD was higher in myometrium than all uterine fibroid groups (small, P = 0.009; inner, P = 0.01; outer, P = 0.01) using U. europaeus lectin, than both regions of large (inner, P = 0.04; outer, P = 0.02) fibroids using FVIII, and than outer regions of large fibroids using CD31 (P < 0.05). There were significantly larger diameter vessels in myometrium and large fibroids compared with small fibroids using CD34, FVIII and the lectin U. europaeus (P

Decreased plasma tissue factor pathway inhibitor in women taking combined oral contraceptives.

Use of combined oral contraceptives (OC) is associated with a significant risk of thrombosis. The mechanisms of this effect are not clearly defined. Tissue factor pathway inhibitor (TFPI) is a circulating anti-coagulant that inhibits the earliest steps in activation of the extrinsic coagulation pathway. It plays a central role in control of coagulation but its contribution to the thrombotic risk associated with OC has not been assessed. Plasma TFPI antigen and activity, factor VIIa, prothrombin fragments 1&2, von Willebrand antigen, fibrinogen, and low density lipoprotein cholesterol were measured by standard assays in women taking OC (aged 16 to 45 years, n = 40) and age-matched women not taking OC (controls, n = 40). Plasma TFPI antigen did not vary significantly across the menstrual cycle in controls. Women on OC had a 25% reduction in plasma TFPI antigen (median 51.0 ng/ml; 95% confidence intervals [CI] 37.5 to 85.5; control 68.0 ng/ml, CI 61.0 to 95.0; P < 0.001) and a 29% reduction in TFPI activity (78.5 U/ml, CI 57.5 to 107.5; control 111.0 U/ml, CI 79.5 to 171.0; P < 0.001) compared to controls. Plasma factor VIIa activity and prothrombin fragments 1&2 were also significantly increased in women using OC (both P < 0.001), indicating activation of the extrinsic coagulation pathway. These results demonstrate that normal cyclic variations in estrogen and/or progesterone do not significantly alter plasma TFPI levels. However, estrogens and/or progestogens in OC result in activation of the extrinsic coagulation pathway and significantly reduce plasma TFPI, its major circulating inhibitor. Reduced plasma TFPI levels may underlie the thrombotic effects of OC.

PIP: This article reports the findings of a study that determined whether use of oral contraceptive (OC) is associated with significant changes in plasma tissue factor pathway inhibitor (TFPI), which may contribute to thrombotic risk. Plasma TFPI antigen and activity, factor VIIa, prothrombin fragments 1 and 2, von Willebrand antigen, fibrinogen, and low density lipoprotein cholesterol were measured by standard assays in 40 women aged 16-45 taking OCs and 40 age-matched women not taking OCs. Results revealed that the plasma TFPI antigen did not vary significantly across the menstrual cycle in controls. Women on OCs had a 25% reduction in plasma TFPI antigen (median, 51.0 ng/ml; 95% confidence interval (CI), 37.5-85.5; controls, 68.0 ng/ml; CI, 61.0-95.0) and a 29% reduction in TFPI activity (78.5 U/ml; CI, 57.5-107.5; controls, 111.0 U/ml; CI, 79.5-171.0) compared to controls. Plasma factor VIIa activity and prothrombin fragments 1 and 2 were also significantly increased in women using OCs, indicating activation of the extrinsic coagulation pathway. These results demonstrate that normal cyclic variations in estrogen and/or progesterone do not significantly alter plasma TFPI levels. However, estrogens and/or progesterone in OCs result in activation of the extrinsic coagulation pathway and significantly reduce plasma TFPI, its major circulation inhibitor. In conclusion, reduced plasma TFPI levels may underlie the thrombotic effects of OCs.

Short- and long-term effects of ovulation induction.

Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone is reviewed. The short- and long-term consequences of these therapies are discussed in detail.

Epidermal growth factor and transforming growth factor-beta in uterine fibroids and myometrium.

Fibroids (leiomyomata) are the commonest tumours in women, but their aetiology is unknown. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF beta) may be important factors involved in fibroid growth. We examined the mRNA expression of these two growth factors in fibroids and corresponding myometrium from 20 women who underwent hysterectomy because of fibroids. We also examined these factors in samples of fibroids from 9 women who underwent myomectomy after pretreatment with luteinizing hormone-releasing hormone agonists. We found that both factors were expressed in the three types of tissue examined. We also found that there was no difference in the relative abundance of either of the two growth factors between the tissues studied. Despite the lack of difference, we postulate that EGF and TGF beta may be important in fibroid growth because of a possible interaction between the two factors in this tissue.

Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin-releasing hormone agonist pretreated women.

OBJECTIVE: The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin-releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR. DESIGN: Cytosolic ER and PR binding was assessed by the dextran-coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA. PATIENTS: Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa. RESULTS: We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and in fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours. CONCLUSIONS: We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding.

Messenger RNA encoding the insulin-like growth factors and their binding proteins, in women with fibroids, pretreated with luteinizing hormone-releasing hormone agonists.

The primary objective of this study was to suggest a possible mechanism of action of luteinizing hormone-releasing hormone agonist (LHRHa) on fibroids. This was performed by investigating insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-1, -2 and -3 mRNA expression in uterine fibroids from women rendered hypo-oestrogenic by LHRHa, using Northern blot analysis. Nine women with fibroids, who were rendered hypo-oestrogenic from at least 4 months pretreatment with LHRHa therapy prior to undergoing myomectomy were investigated. Our results showed that IGF-I, IGF-II, IGFBP-2 and -3 mRNAs were expressed in uterine fibroids, and that IGFBP-1 mRNA or protein was not detected in fibroids. Western ligand blotting showed the presence of IGFBP-2 and -3 proteins, and when compared with a group of women with fibroids not treated with LHRHa (B.J. Vollenhoven et al., 1993, J. Clin. Endocrinol. Metab., 76, 1106-1110) we found that there was no difference in the relative abundance for each of the factors between the two groups of women. Therefore, LHRHa act to decrease fibroid size via induction of a hypo-oestrogenic state rather than by changes in the IGFs and their IGFBPs.

Messenger ribonucleic acid expression of the insulin-like growth factors and their binding proteins in uterine fibroids and myometrium.

Fibroids (leiomyomata) are the most common tumors in women, but their etiology is unknown. The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important in the growth of these benign neoplasms. We have examined the presence of mRNA encoding both IGF-I and IGF-II and IGFBP-1, -2, and -3 in fibroids and corresponding myometrium from 20 women undergoing hysterectomy for symptomatic uterine fibroids. Northern blots of total cellular RNA were probed with oligonucleotides for IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and a human IGFBP-1 cDNA. Western ligand blotting was also used to detect the presence of IGFBP proteins in both fibroid and myometrium. The data showed that in fibroids compared to myometrium, 1) the relative abundance of IGF-I mRNA was not different, but there was an increase in the relative abundance of IGF-II mRNA (P < 0.001); 2) IGFBP-1 mRNA was undetectable in fibroids and detectable in only 1 specimen of myometrium; 3) there was no difference in the relative abundance of IGFBP-2 mRNA, but there was an increase in the relative abundance of IGFBP-3 mRNA in myometrium (P < 0.05). By Western ligand blotting, both IGFBP-2 and -3 proteins were present. Our data show that the mRNAs encoding IGF-I, IGF-II, IGFBP-2, and IGFBP-3 are expressed in both fibroids and myometrium and that fibroids express more IGF-II and less IGFBP-3 mRNA than myometrium. We postulate that the net effect of the changes seen is to increase the bioavailability of free (bioactive) IGF, which may then play a major role in promoting fibroid tumor growth.

An open study of luteinizing hormone releasing hormone agonists in infertile women with uterine fibroids.

Twenty infertile women with fibroids were treated with luteinizing hormone releasing hormone agonists (LHRHa) to investigate if the use of these drugs, both with and without myomectomy, was effective in contributing to pregnancy in these women. All women had fibroids as their sole cause for infertility. Seven women conceived within 1 year of myomectomy or LHRHa treatment alone without myomectomy. The overall pregnancy rate was 36% and the postmyomectomy pregnancy rate was 50%. Initial fibroid size and extent of fibroid shrinkage on LHRHa therapy made no difference to the subsequent pregnancy rate. We also found no significant interaction between the number of fibroids present and the effect of myomectomy on the proportion of pregnancies. We conclude that the fertility enhancing value of myomectomy in otherwise idiopathic infertility is confirmed, and that the use of LHRHa premyomectomy in infertile women needs to be investigated in randomized controlled trials to assess its value as a preoperative therapy.

Clinical predictors for buserelin acetate treatment of uterine fibroids: a prospective study of 40 women.

Buserelin acetate, a luteinizing hormone-releasing hormone agonist, is known to be effective in the shrinkage of uterine fibroids. A prospective trial was undertaken (1) to compare the efficacy of intranasal (IN) and subcutaneous (SC) administration of buserelin acetate and (2) to assess if tumor regression correlated with fibroid size and/or patient age. Forty patients were randomly allocated to receive 6 months of either IN buserelin acetate (n = 21) or SC buserelin acetate (n = 19). Four patients did not complete the study and were excluded from statistical analysis. Fibroid regression occurred in all 36 patients. Overall regression to 66% or less of the initial fibroid volume occurred in 70% of subjects. There was no significant difference in fibroid shrinkage between the two administration routes. A significant positive correlation was found between initial fibroid size and subsequent fibroid regression, with larger tumors being more likely to shrink than smaller fibroids. No correlation was found between the patient's age and the extent of fibroid regression.