Women Undergoing In Vitro Fertilization Treatment Research Articles

Understanding the fertility-related quality of life of women undergoing IVF treatment and how cultural beliefs shaped their treatment experience, outcome expectations and emotional reactions

This study aims to investigate the impact of treatment procedures on the fertility-related quality of life in women undergoing in vitro fertilization (IVF) treatment procedures, how their personal beliefs affect treatment expectations, and cultural factors influencing their reactions at times of implantation failure.

Hospital mental health admissions in women after unsuccessful infertility treatment and in vitro fertilization: an Australian population-based cohort study.

ObjectiveTo examine the association between in vitro fertilization (IVF) and later admission to hospital with a mental health diagnosis in women who remained childless after infertility treatment.MethodsThis was a population-based cohort study using linked administrative hospital and registry data. The study population included all women commencing hospital treatment for infertility in Western Australia between the years 1982 and 2002 aged 20–44 years at treatment commencement who did not have a recorded birth by the end of follow-up (15 August 2010) and did not have a hospital mental health admission prior to the first infertility admission (n=6,567). Of these, 2,623 women had IVF and 3,944 did not. We used multivariate Cox regression modeling of mental health admissions and compared women undergoing IVF treatment with women having infertility treatment but not IVF.ResultsOver an average of 17 years of follow-up, 411 women in the cohort were admitted to hospital with a mental health diagnosis; 93 who had IVF and 318 who did not. The unadjusted hazard ratio (HR) for a hospital mental health admission comparing women who had IVF with those receiving other infertility treatment was 0.50 (95% confidence interval [CI] 0.40–0.63). After adjustment for age, calendar year and socio-economic status the HR was 0.56 (95% CI 0.44–0.71).ConclusionsIVF treatment is associated with a reduced risk of hospital mental health admissions in women after unsuccessful infertility treatment. This may be explained by the healthy cohort effect.

A randomised controlled trial of a preconceptional dietary intervention in women undergoing IVF treatment (PREPARE trial).

BackgroundIn vitro fertilisation (IVF) treatment provides an opportunity to study early developmental responses to periconceptional dietary interventions. Retrospective studies have suggested links between preconception diet and fertility, and more recently, a "Mediterranean" diet has been reported to increase pregnancy rates by up to 40%. In addition, a prospective study examining increased intake of omega-3 polyunsaturated fats demonstrated a quickened rate of embryo development after IVF. However, up to now, few prospective randomised controlled trials have investigated the impact of periconceptional dietary interventions on fertility outcomes.Methods and designThe study is a randomised controlled trial of a dietary intervention consisting of olive oil for cooking, an olive oil based spread, and a daily supplement drink enriched with Vitamin D (10 microgram daily) and marine omega-3 fatty acids (2 g daily) for 6 weeks preconception versus a control diet of sunflower seed oil for cooking, a sunflower oil based spread, and a daily supplement drink without added Vitamin D or marine omega-3 fatty acids. Couples undergoing IVF will be randomised to either the intervention or control group (55 in each arm). The primary endpoint is embryo developmental competency in vitro, measured by validated morphokinetic markers. Secondary outcomes will include the effect of the dietary intervention on the nutritional content of the intrauterine environment.DiscussionThis approach will enable rigorous examination of the impact of the dietary intervention on early embryo development, together with the influence of the peri-implantation intra-uterine nutritional environment.Trial registrationISRCTN50956936

The Effect of In Vitro Fertilization Treatment on Women's Voice

To examine the effect of in vitro fertilization (IVF) treatment on acoustic properties of women's voice. Prospective case series. Ten women undergoing IVF treatment participated in the study. All participants were recorded repeatedly in three successive sessions, before and during treatment, in addition to collecting hormonal assays, endometrial thickness measurements, and follicular growth data. Recordings were performed while sustaining an isolated vowel repeatedly and during a reading task. Acoustic analyses included a limited set of fundamental frequency (F0) measures, as well as frequency- and amplitude perturbation measures. Repeated-measure analyses of variance were performed to test for the treatment effect, and the correlations between the acoustic measures and the hormonal as well as endometrial thickness data were examined. A significant reduction in the two F0 measures and in the amplitude perturbation measure was found throughout the treatment (P<0.05). Before treatment, a negative correlation was found between F0 and estrogen levels. After treatment, however, a negative correlation was found between F0 and endometrial thickness. An association was found between IVF treatment and specific voice properties. In addition, the possibility of a ceiling effect for the influence of estrogens on female vocal folds was introduced.

Kisspeptin: a novel physiological trigger for oocyte maturation in in-vitro fertilisation treatment

BackgroundAlthough in-vitro fertilisation (IVF) treatment allows infertile couples to conceive, it can result in a potentially life-threatening condition termed the ovarian hyperstimulation syndrome (OHSS). The major cause of OHSS is use of human chorionic gonadotropin (hCG) in current IVF protocols for initiating oocyte maturation. The development of a more physiological stimulus for oocyte maturation would avoid this dangerous side-effect and thus improve safety of IVF treatment. Kisspeptin is a recently identified hypothalamic hormone that acutely and potently increases endogenous secretion of luteinising hormone in a gonadotropin-releasing hormone (GnRH)-dependent manner. We aimed to investigate whether kisspeptin can induce oocyte maturation in IVF treatment. MethodsIn this single-centre prospective clinical trial at Hammersmith Hospital, London, women were recruited with the following inclusion criteria: age 18–35 years, body mass index less than 30 kg/m2, serum anti-Mullerian hormone 10–40 pmol/L, and no more than one previous IVF cycle. They underwent a recombinant follicle stimulating hormone plus GnRH antagonist IVF protocol with a single subcutaneous injection of kisspeptin. A control group was not recruited for ethical reasons. Primary outcome was production of mature oocytes (metaphase II oocytes) after egg collection. Participants and doctors giving IVF treatment were masked to the dose of kisspeptin administered. Women were independently randomised by the study statistician, initially to the lowest tier of kisspeptin doses (1·6 or 3·2 nmol/kg, n=2–3 per dose) and then as per protocol to a higher tier of doses (6·4 or 12·8 nmol/kg, n=21 per dose). Oocyte retrieval was done 36 h after kisspeptin injection. After intracytoplasmic sperm injection (ICSI) one or two embryos were transferred to the woman and pregnancy testing done 12 days later. Clinical pregnancy was confirmed on ultrasound scan at 6 weeks of gestation. Multiple means were compared by use of one-way ANOVA with post-hoc Bonferroni correction. Proportions were compared by χ2 test. All data were analysed on an intention-to-treat basis. Women gave written informed consent. The study received approval from the Hammersmith and Queen Charlottes Research Ethics Committee (application number 10/H0707/2) and the Medicines and Healthcare Products Regulatory Agency. The trial is registered with ClinicalTrials.gov, number NCT01667406. FindingsUp to Sept 1, 2013, 47 women completed the study protocol. All doses of kisspeptin resulted in a mean 9·0-fold (SD 7·5) increase in luteinising hormone release 12 h after injection. Oocyte maturation was observed at all doses of kisspeptin. 45 women (96%) had oocyte maturation (mean number of metaphase II oocytes 7·9, SD 4·1). Embryogenesis occurred in 43 women (91%) after treatment with kisspeptin (mean number of zygotes 5·7, SD 3·5). Complete pregnancy data are awaited, but up to Sept 1, 2013, 16 (36%) of 44 women had a positive pregnancy test at 12 days post embryo transfer and ten (23%) had clinical pregnancy confirmed on ultrasound examination at 6 weeks of gestation. Clinical follow-up during pregnancy is continuing, but already the first participant to have received kisspeptin to induce oocyte maturation gave birth to a healthy baby boy in May, 2013. No adverse events were noted at any time during the study. InterpretationThe results of this study suggest, for the first time, to our knowledge, that kisspeptin induces oocyte maturation in women undergoing IVF treatment. Kisspeptin might therefore offer a novel therapeutic option for fertility treatment. This small pilot study provides proof of concept that kisspeptin can stimulate oocyte maturation in women undergoing IVF treatment. Further work is now underway in a larger number of patients to determine the optimum protocol for kisspeptin administration to induce oocyte maturation in a population at high risk of OHSS. FundingUK Medical Research Council, National Institute for Health Research.

Association between in-vitro fertilization, birth and melanoma

A link between reproductive hormones and melanoma has long been suspected, and has been examined for numerous hormonal exposures, but the association between in-vitro fertilization (IVF) and melanoma has not been studied in depth. We used whole-population linked hospital and registry data to carry out a cohort study of women aged 20-44 years seeking hospital investigation and treatment for infertility in Western Australia from 1982 to 2002 with follow-up to 2010. The cohort comprised a total of 21 604 women followed for an average of 17.2 years. Of these, 7524 had IVF treatment, 14 870 gave birth and 149 women were diagnosed with an incident invasive melanoma. Using Cox regression analysis, we estimated hazard ratios (HRs) for melanoma associated with IVF and parity. Women who had IVF and gave birth had an increased rate of invasive melanoma compared with women who had IVF and remained nulliparous (HR 3.61; 95% confidence interval 1.79-7.26). There was little or no increase in the rate of invasive melanoma associated with giving birth in women who had non-IVF infertility treatment (HR 1.39; 95% confidence interval 0.88-2.20). These results suggest an association between reproductive factors and melanoma in the subgroup of women undergoing IVF treatment.

The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta‐analysis

Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. To explore the association between endometriosis and IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment.

A case of empty follicle syndrome who conceived after aspiration of an endometrial cyst.

Empty follicle syndrome (EFS) has been defined as a condition where no oocytes can be retrieved for in vitro fertilization (IVF) even though ultrasound findings and estradiol (E2) levels suggest the presence of potential follicles. The EFS is a rare condition with an incidence of 0.5-7 % of women undergoing IVF treatments. Although there are many hypotheses as to the cause of EFS, including advanced ovarian age, drug-related problems, and dysfunctional folliculogenesis, its cause remains unknown. A 37-year-old woman with endometriosis and a 5-year history of primary infertility underwent IVF treatment for 4 cycles. No oocytes were retrieved in 2 cycles and no fertilized eggs were obtained in the other 2 cycles. We assumed that endometriosis adversely affected folliculogenesis and fertilization. Aspiration of an endometrial cyst in the right ovary and subsequent administration of oral contraceptives resulted in successful folliculogenesis and fertilization. Thereafter, she conceived and delivered a 2,662 g female infant at 38 weeks of gestation. Here, we report a case of EFS who conceived in the 5th IVF cycle after aspiration of an endometrial cyst. We assumed that endometriosis might have been involved in the dysfunction of folliculogenesis and EFS.

Clomiphene citrate in combination with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilization

Gonadotropins are the most commonly used medication for controlled ovarian stimulation in in vitro fertilization (IVF). However, they are expensive, invasive and are associated with risk of ovarian hyperstimulation syndrome (OHSS). With recent calls for patient friendly IVF, there has been an interest in the use of clomiphene citrate with or without gonadotropins to reduce the burden of injections. However, it is not known whether regimens using clomiphene are at least as effective as gonadotropins alone. To determine whether clomiphene citrate with gonadotropins (with or without mid-cycle antagonist) is more effective than gonadotropins with gonadotropin-releasing hormone (GnRH) agonists for controlled ovarian stimulation in IVF or intracytoplasmic sperm injection (ICSI) treatment. Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched March 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, first quarter), MEDLINE (1970 to March 2012), EMBASE (1985 to Mar 2012) and reference lists of articles. Relevant conference proceedings were handsearched. Randomised controlled trials (RCT) were included. Live birth rate (LBR) per woman was the primary outcome. Two review authors independently assessed the eligibility and quality of trials Fourteen studies were included in the review. Meta-analysis could be performed with the data of 12 included studies, with a total of 2536 participants. There was no evidence that clomiphene along with gonadotropins for IVF, with or without mid-cycle GnRH antagonist, differed from gonadotropins alone in GnRH agonist protocols in terms of live births (5 RCTs, 1079 women; OR 0.93, 95% CI 0.69 to1.24) or clinical pregnancy (11 RCTs, 1864 women; OR 1.07, 95% CI 0.85 to1.33). This means that for a typical clinic with 23% LBR using a GnRH agonist regimen, switching to clomiphene protocols would be expected to result in LBRs between 16% and 26%. There was a significant reduction in the incidence of OHSS (5 RCTs, 1559 women; OR 0.23, 95% CI 0.10 to 0.52). This means that for a typical clinic with 3.5% prevalence of OHSS using a GnRH agonist regimen, switching to clomiphene citrate protocols would be expected to reduce the incidence to between 0.8% and 1.8%. The trials included in this review were very old and outcomes such as live births, multiple pregnancy, OHSS and miscarriages have not been reported by most studies. There was no evidence to indicate that clomiphene with gonadotropins (with or without GnRH antagonist) differed significantly from gonadotropins in GnRH agonist protocols for women undergoing IVF treatment, in terms of live births or pregnancy rates. Meanwhile, use of clomiphene led to a reduction in the incidence of OHSS. However, these results were based on data from a small number of underpowered randomised trials with few participants. Hence there was insufficient evidence to recommend use of clomiphene citrate in routine IVF practice. Larger trials with adequate power are required.

Protein and Steroid Profiles in Follicular Fluid after Ovarian Hyperstimulation as Potential Biomarkers of IVF Outcome

Controlled ovarian hyperstimulation is performed to assist with generation of multiple mature oocytes for use in in vitro fertilization (IVF). The goal of our study was to evaluate differences in protein and steroid profiles in ovarian follicular fluid (hFF) samples obtained during oocyte retrieval from women undergoing IVF treatment and to identify physiological pathways associated with the proteins. The hFF samples were depleted of abundant proteins, fractionated by ultrafiltration, digested, and analyzed by nano-LC-QTOF. Concentrations of 15 endogenous steroids were determined in the samples using LC-MS/MS methods. The total number of proteins identified in the samples was 75, of which 4, 7, and 2 were unique to the samples from women with viable pregnancy, miscarriage, and no pregnancy, respectively. Identified proteins were associated with the acute response signaling, coagulation system, intrinsic and extrinsic prothrombin activation, complement system, neuroprotective role of THOP1, FXR/RXR activation, role of tissue factor, and growth hormone pathways. A greater number of proteins associated with biosynthesis was found in hFF samples corresponding to the oocytes resulting in pregnancy. The abundance of seven proteins was found to be associated with steroidogenesis. The obtained data will contribute to better understanding of the pathogenesis and development of noninvasive markers for assessment of oocytes viability.

An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome

To determine whether metabolomic analysis of follicular fluid could prove a useful noninvasive technique for the selection of viable oocytes and embryos. Metabolomic analysis based on proton nuclear magnetic resonance ((1)H NMR) performed on follicular fluid collected from in vitro fertilization (IVF) patients. A university research center and a private fertility clinic. Fifty-eight women undergoing IVF treatment. Follicular fluid collected at the time of oocyte retrieval. Metabolomic profile, assessment of oocyte developmental potential and embryo viability. The metabolomic profile of follicular fluid from follicles where the oocyte resulted in a fertilized egg that failed to cleave (n = 9) was distinctly different from that where oocytes developed into early cleavage-stage embryos. Discriminating metabolites included glucose, lactate, choline/phosphocholine, and lipoproteins. Comparison of follicular fluid from women who subsequently had a positive β human chorionic gonadotropin (n = 10) to those who were unsuccessful in achieving a pregnancy (n = 12) revealed metabolic differences that were correlated to cycle outcome. Differences in the metabolite composition of follicular fluid correlate with the developmental competence of the human oocyte. Therefore, metabolomic profiling of follicular fluid may prove to be an important technique in gamete/embryo selection.

Serum and follicular fluid anti-mullerian hormone concentrations at the time of follicle puncture and reproductive outcome

The objective of the study is to determine and compare the levels of Anti-Mullerian hormone (AMH) and estradiol (E2) in serum and follicular fluid (FF) on the day of oocyte pick up (OPU) with the cycle parameters and the outcome of in vitro fertilization (IVF) treatment. The long stimulation protocol was used in 37 (86%) women; the microdose flare-up protocol was used in 6 (14%) women. Concentrations of AMH and E2 were measured in serum and FF of 43 women undergoing IVF treatment on the day of OPU. Significant positive associations were observed between serum AMH concentrations and the total number of oocytes retrieved (r=0.343, p=0.024). Serum AMH and FF AMH levels on the day of OPU were significantly increased in the group of women who achieved clinical pregnancy (p=0.017, p=0.028). For serum AMH, a cut-off level of 1.64 ng/ml was used for the prediction of clinical pregnancy; for FF AMH, a cut-off level of 3.8 ng/ml was used for the prediction of clinical pregnancy. Serum AMH and FF AMH levels were significantly and positively correlated with implantation rate (r=0.401, p=0.008; r=0.317, p=0.039). No significant correlation was found between serum and FF AMH concentrations and fertilization rate. Serum AMH and FF AMH concentrations are positively correlated with implantation and clinical pregnancy rates.

Does catheter choice during embryo transfer alter the pregnancy rate?

Although every step in the in vitro fertilisation (IVF) procedure is important, the impact of embryo transfer (ET) on pregnancy rate (PR) is significant. Of all the crucial aspects of ET the type of catheter used and the technique of transfer on the PR has drawn the maximum attention and controversy. We aimed to compare the outcome of two different ET catheters on the PR. A prospective analysis comparing the classical Frydman (Laboratoire CCD, France) and the soft Cook (Cook Medical, Indiana, USA) ET catheters was performed. Primary end-point was clinical pregnancy rate (CPR); secondary end-points were rates of difficult transfer. A total of 1,446 ETs were performed in women undergoing IVF treatment, of which 723 cycles were randomised to the Cook catheter and 723 to the Frydman catheter. It was observed that, although the Cook catheter was related to a slightly higher PR, the overall comparison failed to indicate a significant difference in CPR. It was also seen that the ease of transfer did not significantly affect the PRs. Individual variables during ET may not contribute significantly to the success of an IVF programme; however, a holistic approach encompassing all the factors is quintessential to improve the PR.

The “Lived Pain” Experience: The Case of Women Undergoing IVF treatments

This research used the embodied approach to analyse the pain experiences of 25 heterosexually married Israeli-Jewish women undergoing in vitro fertilization (IVF) treatments for a first pregnancy. Semi-structured interviews were conducted to allow the women to openly discuss issues concerning their perceptions of pain. Research findings show that the women’s pain perceptions dictated two distinct categories of discourse. The first category of discourse surfaced in the accounts of 14 of the interviewees. Women belonging to this category expressed their willingness to “do everything for a child”. These women insisted on silencing pain and considered it to be irrelevant. They refused to locate bodily pains at the centre of their experience, fearing that this would delay their goal of reproducing. The second discourse of pain emerged from the accounts of 11 interviewees. This discourse was associated with women’s motivation to maintain an active dialogue with painful experiences. They obstinately sought to direct internal attentiveness to what was happening inside their bodies. This approach enabled them to define body boundaries and form an active negotiation with the authority treating their bodies. The research findings suggest that women who share the same socio- cultural environment (Israeli pronatalism) and physical circumstances (the inability to conceive) have varied and wideranging interpretations of pain. It seems that medical authorities can benefit the understanding of pain by providing new support resources to women undergoing IVF treatments.

The Psychological Needs of Women Undergoing IVF Treatment

Assisted reproductive technology (ART) research has achieved a breakthrough in the understanding of natural reproductive processes and their possible ineffective outcomes. In Vitro Fertilization (IVF) has succeeded in treating chronic fertility problems that could not be solved by routine interventions. IVF reaped its first success in 1978, with the birth of the world's first ‘test-tube baby’: Louise Joy Brown's birth indeed confirmed the feasibility of retrieving ova from the follicles, inseminating them under laboratory conditions, transferring the fertilized ova to the patient's uterus and supporting their implantation. IVF opened a new era in the treatment of infertility, offering hope to women and couples who otherwise would have remained childless. Yet this technological achievement has given rise to controversy on ethical issues and questions about the legal rights to apply modern reproductive technologies. The legal and public debates surrounding IVF treatment started long before the day-to-day experiences of IVF patients received any in-depth attention. Hence, the experiences of women undergoing IVF treatment remained largely external to the bioethical debate. In the present article, I shall claim that understanding the female experience is an essential element in the bioethical debate on IVF. This claim is valid regardless of whether the problem treated originates in the woman or her male partner, as in either case the woman is the one undergoing the surgical procedure. The present article summarizes research on the experiences of IVF-treated women in Israel, and discusses the relevance of this research's findings to the bioethical debate in this respect.

Estradiol supplementation during the luteal phase of in vitro fertilization cycles: a prospective randomised study

ObjectiveTo find the optimal dosage of estradiol (E2) for luteal phase support through the addition of different doses of E2 to progeserone (P) luteal phase support in patients undergoing long GnRH agonist in vitro fertilization (IVF) treatments. Study designTwo hundred and eighty-five women undergoing IVF treatment with a long GnRH agonist protocol were prospectively randomized into three groups. Group 1 (n=95) received P and 2mg E2, group 2 (n=95) received P and 4mg E2 and group 3 (n=95) received P and 6mg E2 as luteal phase support. The primary outcome was the clinical pregnancy rate (PR). The secondary variables of interest were the implantation rate (IR), miscarriage rate and multiple PR. ResultsThe clinical PR was 31.6%, 40% and 32% respectively in groups 1, 2 and 3 and the differences between groups were not statistically significant. However, the miscarriage rate was significantly lower in group 2 (2.6%) than in group 1 (20%) but was not significantly lower than in group 3 (9.6%). ConclusionFor luteal phase support, adding 2, 4 or 6mg of oral E2 to P creates no statistical difference in terms of pregnancy rates. However, a significantly higher miscarriage rate was found when 2mg E2 was used. Therefore, in the luteal phase support, 4mg of oral estradiol in addition to progesterone can be considered to reduce the miscarriage rate. CondensationFor luteal phase support, adding 2, 4 or 6mg of oral estradiol to progesterone showed no statistical difference in terms of pregnancy and implantation rates, but a significantly higher miscarriage rate was found when 2mg estradiol was used.

Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years

Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment. This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred. There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little. The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

The Effect of Temporary Elevated 17 B Estradiol (E2) Levels On the Coagulation System as Measured by D-Dimer in Women Undergoing in Vitro Fertilization.

Abstract 4004Poster Board III-940 BackgroundHyperestrogenic conditions of long duration such as pregnancy, use of oral contraceptives and estrogen replacement therapy have been related to alterations in the coagulation parameters and are considered as risk factors for increased incidence of thromboembolic events. In vitro fertilization (IVF) involves the use of exogenous hormones to achieve cycle control, stimulate the ovaries, and support implantation. During this process the 17 B estradiol (E2) levels change from minimal to supraphysiological levels in the same patient over several weeks. The ovarian stimulation usually continues for 8-14 days and as a result the estrogen levels are high for a relatively short time. D-dimer, a fibrin degradation product, is a marker of hypercoagulable states and of endogenous fibrinolysis. Quantitative D-dimer testing is routinely used in clinical management for its high negative predictive value in suspected venous thromboembolism, especially, in an emergency room setting. There are several reports of progressive increase of D- dimer levels (>0.5 ng/ml) during normal pregnancy and there have been reports of thromboembolic complications in patients undergoing IVF. Therefore, patients undergoing IVF present an opportunity to study isolated estrogen effects on the coagulation system. ObjectiveThe aim of our study was to evaluate the effect of short term elevated estrogen blood levels on the coagulation system as measured by D-dimer in women undergoing IVF. Methods62 healthy women under age of 40, who were scheduled to undergo IVF were included in the study. Induction of ovulation was performed in all patients with standard long protocol using GnRH agonist. Blood samples were obtained at baseline, maximum down regulation (E2<200 pmol/l) and on the day of oocyte retrieval. Plasma D-dimer level was measured by VIDAS ELISA assay according to the hematology laboratory standard protocol. D-dimer level below 500 ng/ml was considered a normal value. Results47/62 recruited subjects met the protocol requirements. The mean age of the participants was 28.6 years (range 20-39) and their mean BMI was 26 (range 18-38). Serum E2 concentrations (mean ±SD) on down regulation day and at oocyte retrieval day were 125±36 and 6549 ±3803 pmol/L respectively. Plasma D-dimer level (mean ±SD) on down regulation day and at oocyte retrieval day was 208 ±84 and 245±129 ng/ml respectively. There was a 21% increase in D-dimer (p<0.024) in the entire group. There was a statistically significant increase in D-dimer level in women with BMI >30 as compared to women with BMI <30 (38.5%/ 18.8%; p=0.06). However, in none of the groups did the level of D-dimer exceed the normal cut off value. There was no correlation between E2 levels and the level of D-dimer. Pregnancy rate was 47.5% per transfer and there was no significant correlation between pregnancy rate and the level of D-dimer. ConclusionIn our study of healthy women undergoing IVF, we found that short term exposure to supraphysiological level of E2 for induction of ovulation caused a significant increase in D-dimer level; however, it remained within the normal value. We conclude that short term exposure to supraphysiological level of E2 did not affect thromboembolic status as expressed by D -dimer levels. This may not apply to states of long term exposure to elevated E2. The finding of positive correlation of levels of D-dimer with BMI may indicate that overweight women undergoing IVF treatment may have a contributing risk factor for thromboembolic events. Further studies of larger groups are warranted to confirm our findings. Disclosures:No relevant conflicts of interest to declare.

The effect of the in vitro fertilization (IVF) medication on endometrial natural killer cell (NK Cell), β3 integrin and Cyclin E

OBJECTIVE: The purpose of this pilot study is to see if the use of fertility medications in women undergoing IVF treatments have any significant effect on: 1) Natural Killer Cells at the level of the Endometrium and in peripheral blood 2) The Endometrial Expression of ß3 Integrin and Cyclin E.

503. SUCCESSFUL IN VITRO FERTILIZATION (IVF) AFTER PRIOR FAILED IVF UTILIZING A PROPRIETARY BLEND OF SUPPLEMENTS

Background: To date, little is known about the effect of supplements on the outcome of in vitro fertilization (IVF). The data on this matter is limited to measuring the overall pregnancy rate on a population of women who took a specific supplement, and not on IVF patients. Objectives: To demonstrate the positive role of an investigated supplement in the outcome of patients undergoing IVF. Method: 18 women undergoing IVF treatment were placed on a proprietary combination of vitamins and antioxidants designed to encourage blood flow and improve egg quality. The women were selected for this protocol mostly due to prior poor egg quality and/or large amount of embryo fragmentation .The women took supplementation twice daily for 4–12 weeks prior to transfer. The charts of the patients who used the supplements were used to obtain data. Previous failed IVF was defined as negative pregnancy. Successful IVF outcome was determined by positive chemical pregnancy and clinical pregnancy after one attempt. Range and mean was calculated for patient's age and number of failed previous IVF attempts. The previous IVF attempts were performed in different centers without using this supplement in all patients. Results: Eighteen patients used the supplement before and during their IVF cycles. Patient's age ranged from 28 to 44 with mean of 36.4 years. They had on average, 2 prior failed IVF attempts. Seventeen of 18 patients had successful IVF outcome. The failed patient required frozen testicular extraction of sperm (TESE), prior to IVF. Summary: Seventeen of 18 patients who used our supplements had successful IVF. These patients failed an average of 2 previous IVF attempts without using our supplements. Conclusion: Usage of our supplements is associated with improved rates of success in patients undergoing IVF with a history of prior failed IVF attempts. Larger studies need to be conducted.