Day Of Pregnancy Test Research Articles

The impact of extremely brief meditation and brief mindfulness interventions on assisted reproductive technologies success rates: A randomised controlled trial

ObjectiveTo investigate the effect of extremely brief meditation (EBMI) or brief mindfulness interventions (Brief MI) on pregnancy rate in women undergoing Assisted Reproductive Technology (ART). MethodsThis is a prospective, three-armed, randomized controlled trial with women undergoing ART cycle, age ranging from 18 to 50 years. In the day of embryo transfer, the patients randomized to Brief MI group received a 15-minute audio of mindfulness. They were instructed to practice it daily, starting from the day of embryo transfer to the day of the pregnancy test, leading to a total of 180–210 minutes. Women randomized to EBMI met once a week during the waiting time between the embryo transfer and pregnancy test day in the same virtual room with a meditator instructor for 40 minutes, totalizing two sessions (80 minutes). The pregnancy rate was assessed via a blood test to measure hCG performed 2 weeks after embryo transfer. ResultsA total of 68 women aged 37.5 ± 4.3y were included (EBMI, n = 24; Brief MI, n = 22 and CG, n = 22). Pearson's Chi-square test and Student's t-test for independent samples showed no significant differences between intervention and control groups. Both EBMI and Brief MI had no significant effect on pregnancy rate in women undergoing ART. ConclusionThis randomized control trial revealed that the extremely brief meditation (EBMI) or self-managed brief mindfulness intervention (Brief MI) had no significant effect on pregnancy rates in infertile women undergoing ART cycles. Trial registration number: NCT04058262.

Perceived stress reduction through an infertility coaching program: a randomized controlled clinical trial

Infertility has been recognized as a distressing experience among couples worldwide, cutting across various cultures. This present study was conducted to assess the impact of a supportive stress management program led by an infertility coach for women undergoing fertility treatment. This randomized controlled clinical trial study was performed on 60 infertile women undergoing assisted reproductive techniques at Maryam Infertility Center located in Sari in 2018. After random allocation in two groups, 30 individuals were in the intervention group and 30 in the control group. The intervention program was implemented according to the infertility coach's counseling protocol in six stages. The control group received only routine ward counseling. In order to measure stress, the Newton Infertility Stress Questionnaire was used firstly before intervention and then after oocyte puncture, embryo transfer, and pregnancy testing. Data analysis was performed using SPSS statistical software version 18 and Shapiro–Wilk, Chi-square, Mann–Whitney, independent t-test, Friedman test, Wilcoxon test, GEE test, and Cohen's effect size. Our analysis approach has also been based on the analysis of (ITT). The significance level was 0.05. The mean ± SD scores of infertility perceived stress before the intervention in the control was 146.16 ± 16.90 and the intervention group was 156.53 ± 9.31, after intervention at the time of oocyte puncture in the controls was 165.36 ± 8.98 and the intervention group was 155.83 ± 10.70, at the day of embryo transfer in the control group was 156.35 ± 14.45 and in the intervention group was 123.58 ± 22.9 and in the pregnancy test day in the control group was 185.76 ± 26.56 and in the intervention group was 127.61 ± 21.57 (P < 0.001). According to Friedman test, the mean of stress in three situations after the intervention showed a significant difference in reduction of the mean of stress (P < 0.001). In the control group, the stress score of the samples had an increasing trend, which was significant during the measurement steps based on Friedman test results (P < 0.001). In the intervention group, paired t-test results showed no significant comparing mean score of Newton's infertility stress before and after oocyte puncture day (P = 0.711), comparing the mean of stress before and after pregnancy test day (P = 0.003) and also comparing of mean stress before and after pregnancy on the day of embryo transfer according to Wilcoxon test (P < 0.001). And comparing mean stress before and after pregnancy test day, paired t-test (P = 0.001) showed significant statistical differences. According to the results of the GEE test, changes in stress scores over time were significant between the two groups (P < 0.001), as well as the effect of stress on oocyte puncture day (0.41), embryo transfer day (1.69), pregnancy test day (P < 0.001) (2.46) had a significant effect on the day of embryo transfer and pregnancy test day. Based on the results of this study, the infertility coach program demonstrated the ability to decrease the perceived stress related to infertility. Additionally, it showed potential in enhancing treatment outcomes, such as oocyte count and positive pregnancy results, among infertile women undergoing assisted reproductive techniques.Trial registration: Iranian Registry for Clinical Trial (the link to trial: https://www.irct.ir/trial/33357). Registered 11-11-2018.

Serum progesterone concentration on pregnancy test day might predict ongoing pregnancy after controlled ovarian stimulation and fresh embryo transfer.

Progesterone (P4) is essential for pregnancy. A controlled ovarian stimulation (COS) leads to a iatrogenic luteal defect that indicates a luteal phase support (LPS) at least until pregnancy test day. Some clinicians continue the LPS until week 8 or later, when P4 is mainly secreted by syncytiotrophoblast cells.Measuring serum P4 on pregnancy test day after a fresh embryo transfer could help to identify women who might benefit from prolonged LPS. In women with LPS based on P4 administered by the rectal route, P4 concentration on pregnancy test day was significantly higher in patients with ongoing pregnancy than in patients with abnormal pregnancy.This monocentric retrospective study used data on 99 consecutive cycles of COS, triggered with human chorionic gonadotropin, followed by fresh embryo transfer resulting in a positive pregnancy test (>100 IU/L) (from November 2020 to November 2022). Patients undergoing preimplantation genetic screening or with ectopic pregnancy were excluded. All patients received standard luteal phase support (i.e. micronized vaginal progesterone 600 mg per day for 15 days). The primary endpoint was P4 concentration at day 15 after oocyte retrieval (pregnancy test day) in women with ongoing pregnancy for >12 weeks and in patients with miscarriage before week 12 of pregnancy.The median P4 concentration [range] at pregnancy test day was higher in women with ongoing pregnancy than in women with miscarriage (55.9 ng/mL [11.6; 290.6] versus 18.1 ng/mL [8.3; 140.9], p = 0.002). A P4 concentration ≥16.5 ng/mL at pregnancy test day was associated with higher ongoing pregnancy rate (OR = 12.5, 95% CI 3.61 - 43.33, p <0.001). A P4 concentration ≥16.5 ng/mL at pregnancy test day was significantly associated with higher live birth rate (OR = 11.88, 95% CI 3.30-42.71, p <0.001).After COS and fresh embryo transfer, the risk of miscarriage is higher in women who discontinue luteal support after 15 days, as recommended, but with P4 concentration <16.5 ng/mL. The benefit of individualized prolonged luteal phase support should be evaluated.

Comparing the effects of two different progesterone vaginal gels, Progeson™ and Crinone™, from pharmacokinetics study to clinical applications in patients undergone fresh embryo transfer and frozen-thawed embryo transfer via natural cycle endometrial preparation protocol.

The pharmacokinetics performance and clinical pregnancy rate of two vaginal progesterone gel, Progeson™ and Crinone™, were compared in this study. In the pharmacokinetics performance, Progeson showed similar long-term dissolution rate as Crinone. In the clinical study, 141 subjects undergone invitro fertilization (IVF) treatments were included to compare serum progesterone level and clinical pregnancy rates. Among the subjects, 78 subjects received fresh embryo transfer and 63 subjects received frozen embryo transfer via natural cycle endometrial preparation protocol. In each group, subjects were given either Crinone™ or Progeson™ for luteal phase support without combination with other progesterone products. The study showed that Crinone™ group led to higher estrogen level at mid-luteal phase in the fresh embryo transfer group, and Progeson™ group led to higher progesterone level at mid-luteal phase and pregnancy test day in the frozen-thawed embryo transfer group. Subjects received Crinone™ or Progeson™ had similar rate of pregnancy, live birth, and stillbirth in both fresh embryo transfer and frozen-thawed embryo transfer group. Thus, Progeson™ might be a suitable substitute for Crinone™ in assisted reproductive therapy.

P-362 The association between pregnancy-test day serum progesterone in IVF pregnancies and obstetrical complications

Abstract Study question Is there an association between pregnancy-test day serum progesterone level in IVF pregnancies and late gestational complications? Summary answer Low serum progesterone on pregnancy diagnosis day is independently associated with a higher prevalence of preeclampsia. What is known already Low first trimester arbitrary serum progesterone is associated with early pregnancy complications such as ectopic pregnancies and miscarriages. IVF pregnancies are associated with higher prevalence of obstetrical complications such as preterm birth, preeclampsia and small for gestational age. Different patient and treatment parameters such as age, diagnosis, peak blood Estradiol level, endometrial thickness, fresh or frozen embryo transfer are associated with obstetrical complications. Progesterone is a potent immunomodulator that can affect the inflammatory pathway and trophoblast invasion. Little is known about the association between early pregnancy progesterone level and obstetrical complications, with conflicting results. Study design, size, duration A cohort study reviewing fertility and delivery files of all singleton live births from successfully treated infertile patients, who underwent ovarian stimulation, IVF and fresh embryo transfer in a tertiary medical center between 2008 and 2018. Participants/materials, setting, methods Serum progesterone concentration was measured with the first serum hCG on 4 + 0 gestational week (14 days after oocyte retrieval) under luteal support with vaginal progesterone. Pregnancy-test day serum progesterone was categorized in quartiles. The prevalence of obstetrical complications including gestational diabetes mellitus, preterm birth, preeclamsia, small for gestational age, post-partum hemorrhage and neonatal ICU hospitalization was compared between the four groups. Confounders were adjusted for by multivariate analysis. Main results and the role of chance 719 singleton live births were included. The four serum progesterone quartiles were: Q1:3-44 nmol/L(n = 180); Q2:45-107 nmol/L(n = 180); Q3:108-223 nmol/L(n = 178); Q4:225-808nmol/L(n = 181). Patients with lower progesterone levels (Q1) had significantly more IVF treatments, lower peak estradiol level, fewer mature follicles and frozen embryos. The incidence of preterm labor, gestational diabetes mellitus, small-for-gestational-age, post-partum hemorrhage, placental abruption or neonatal ICU administration did not differ between the groups. Patients with lower serum progesterone had higher incidence of preeclampsia (9.44% in Q1, 2.78% in Q2, 2.81% in Q3 and 3.31% in Q4, P = 0.0046). On multivariate analysis, controlling for age, gravidity, treatment number, number of oocytes, peak follicular estradiol and progesterone, Q1 progesterone level was independently associated with an increased risk of preeclampsia (estimated OR = 3.27 95% CI 1.455-7.299). Limitations, reasons for caution Retrospective design, vaginal progesterone luteal support administration. Wider implications of the findings Low serum progesterone on pregnancy diagnosis day in gestations resulting from fresh ET is associated with a significantly higher prevalence of preeclampsia, possibly because of aberrant placentation and vascular development. This association is important for the obstetrical management, preeclampsia risk assessment, and administration of preventive therapy. Trial registration number not applicable

P-690 Time to bust some myths about progesterone supplementation in the luteal phase. Role of the route of administration and usefulness (or uselessness) of plasma determination

Abstract Study question Is it worth measuring plasma progesterone levels after FET? Is there any difference in results depending on the route of progesterone administration? Summary answer The administration route of progesterone supplementation after FET entails different plasmatic levels (whose determination is useless) but without any correlation with ongoing pregnancy. What is known already Embryonic aneuploidy is likely to be the major contributor to human implantation failure, but not all failures are due to embryonic defects. The need for progesterone supplementation in ART frozen-thawed cycles is well accepted. Several studies have demonstrated an increase in live birth rate with progesterone luteal support although there is a discussion on the association of Progesterone levels on day of embryo transfer and birth or pregnancy loss rates. Moreover, although the effect of route of administration of progesterone on serum levels and pregnancy rates have been thoroughly studied, there is no consensus on the optimal endometrial preparation protocol. Study design, size, duration Prospective, randomized study performed during the 2020-21. A total of 201 genetically screened blastocyst (after PGT-A) transfers were performed after endometrial preparation, performed with exogenous estrogen administration followed by progesterone administration before embryo transfer (ET) . After embryo transfer, two different Progesterone regimens were randomly administered. Group I and Group II (see “Participants”) Participants/materials, setting, methods Group I patients (n = 100): 800 mg of micronized Progesterone was administered vaginally (Cyclogest® 1-0-1). Group II patients (n = 101): vaginal administration of 400 mg of micronized progesterone was combined with the subcutaneous administration of 25 mg of Progesterone (Prolutex 25®) Plasmatic progesterone (PP) levels on day of B-HCG determination (pregnancy test) (10 days after ET) and ultrasound confirmation of pregnancy (3 weeks after ET) were determined. The relationship between progesterone levels and ongoing pregnancy rates was amalyzed. Main results and the role of chance The rate of positive pregnancy test among the 201 FET was 71,64%. The overall ongoing pregnancy was 58,71%. PP on day of pregnancy test was 24,92±1,27 ng/ml (mean±SEM). The corresponding figures por positive (n = 144) and negative (n = 57) HCG were 27,65±1,09 and 20,33±2,13 respectively (t = 2,68; p = 0,008). The PP levels on day of HCG determination were 23,12±1,48 among ongoing pregnancies whereas the levels among non-evolutive gestations were 48,78±3,55 (t = 7,19; p = 0,000). PP levels were significantly higher among group II patients (combined treatment) both, on day of B-HCG determination (28,25±1,22 ng/ml) and on day of ultrasound confirmation of a gestational sac (33,61±2,39) than among group I patients (vaginal treatment) (15,12±1,60 and 19,77±1,50 ng/ml) (t = 0651, p = 0,000 and t = 5,38, p = 0,000 respectively). But these differences do not correlate with ongoing pregnancy rates: 59 out of 101 (58,42%) in group I patients and 59 out of 100 (59%) in group II patients. Limitations, reasons for caution Even though only euploid embryos have been transferred, ee must be cautious when drawing conclusions from the present study taking into account the limited number of cases evaluated. Wider implications of the findings Since only euploid embryos have been transferred in the present study, results in terms of successful ongoing pregnancies may be influenced by endometrial factors. Although the need of progesterone supplementation among frozen-thawed cycles is accepted, some debate exists on the route of administration and the need of progesterone serum determinations Trial registration number NOT applicable

L-Carnitine and Clomiphene Citrate for induction of ovulation in women with Polycystic Ovary Syndrome : Randomized controlled trial

Aim: The aim of the study was to assess the efficacy of adding L-carnitine to clomiphene citrate for increasing the ovulation and the pregnancy rate in women with PCOS. The primary outcome was the ovulation rate and the secondary outcome was the pregnancy rate.Materials and Methods: This study was a randomized controlled clinical trial that was conducted on 94 women who attended at the Obstetrics and Gynecology Outpatient Infertility Clinic at Ain-Shams University Maternity Hospital, and they were diagnosed with PCOS according to the Rotterdam Criteria (11). The women were distributed randomly into two equal groups; Group L (n=47) received 100 mg of clomiphene citrate plus 3 gm of L-carnitine orally from day 3 to day 7 of the cycle with continuation of L-carnitine till the day of pregnancy test and Group C (n=47) received 100 mg of clomiphene citrate orally from day 3 to day 7 of the cycle.Results: There was a significant difference (P 0.05) between the two groups regarding the pregnancy rate (Group L: 8.5%; Group C: 6.4%). There was a highly significant difference (P 0.05) between the two groups regarding the level of progesterone after 8 days from the hCG injection.Conclusion: L-carnitine added to clomiphene citrate for induction of ovulation in PCOS women had a significant effect on the ovulation rate, but it didn’t have a significant effect on the pregnancy rate when compared to clomiphene citrate alone.

Effect of empiric intravenous intralipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial

To evaluate the effect of empiric intralipid infusion therapy on pregnancy outcomes for patients with unexplained recurrent implantation failure (RIF) undergoing intracytoplasmic sperm injection (ICSI). A total of 142 patients with a history of unexplained RIF (3 or more cycles) were included in this randomized controlled trial. Patients were randomized into two groups, study group (n = 71) and control group (n = 71). The study group received intralipid 20% infusion on the day of embryo transfer (ET) and a second dose on the day of pregnancy test. The clinical pregnancy rate in the study group was 36.6% (n = 26) compared to 28.2% (n = 20) in the control group (OR 1.47, CI 0.72–2.98, p = .282). The live birth rate in the study group was 18.3% (n = 13) and 14.1% (n = 10) in the control group (OR 1.37, CI 0.55–3.36, p=.49). No side effects of intralipid therapy were reported in the study period. There was improvement in the pregnancy rate among women with unexplained RIF who received empiric intralipid infusion therapy; however, this improvement did not reach statistical significance.

Progesterone levels on pregnancy test day after hormone replacement therapy-cryopreserved embryo transfer cycles and related reproductive outcomes.

Do serum progesterone levels determine ongoing pregnancy rates (OPR) in hormone replacement therapy frozen-thawed embryo transfer (HRT-FET) cycles? A cohort study of 244 HRT-FET cycles from a Danish public fertility centre. Data from patients undergoing HRT-FET from January 2016 to December 2017 were extracted from a clinical database. All patients had transfer in HRT cycles of autologous embryos frozen on day 5 or 6. Endometrial preparation was performed using 6 mg oestradiol valerate daily from the second day of the cycle followed by vaginal micronized progesterone (90 mg/8 h). All patients had serum progesterone measurement during the artificial luteal phase. The optimal cut-off for ongoing pregnancy was 35 nmol/l based on sensitivity analysis of different progesterone levels as a factor variable and its association with ongoing pregnancy. No significant differences regarding number of embryos transferred, embryo quality, age, body mass index (BMI) or smoking were found in the two groups of progesterone < 35 nmol/l and ≥ 35 nmol/l, respectively. A total of 51% of patients had a serum progesterone < 35 nmol/l. The range of all measurements was 0.3 to 110 nmol/l. The unadjusted OPR was significantly lower in the < 35 nmol/l group compared with the ≥ 35 nmol/l group (38% versus 51%;P = 0.04). A logistic regression analysis, adjusting for smoking, age, BMI, number of embryos transferred and blastocyst age showed a significant decrease in OPR when progesterone was < 35 nmol/l of 44% (95% confidence interval [CI] 35-54%) compared with ≥ 35 nmol/l of 58% (95% CI 48-68%), risk difference of 14% (95% CI 2-26%,P = 0.02). Serum progesterone levels < 35 nmol/l decrease the chance of OPR in HRT-FET cycles.

Gonadotropin-releasing hormone receptor antibody activity over time in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a diagnosis of exclusion with unknown etiology. We recently identified autoantibodies (AAbs) to the second extracellular loop (ECL-2) of the gonadotropin releasing hormone receptor (GnRHR) in a majority of patients with PCOS compared to ovulatory controls in baseline serum measurements. The present assay may represent the desired serological test needed to effectively screen subjects for possible PCOS. Currently, no data exists regarding autoantibody activity over time or with changes in the hormonal milieu associated with infertility treatments, specifically controlled ovarian hyperstimulation (COH) with in vitro fertilization (IVF). To evaluate the levels of AAbs to GnRHR in the serum of eleven subjects with PCOS and infertility over time and observe for changes relative to hormonal fluctuations occurring over the course of infertility treatment. Sera samples from eleven women with PCOS and infertility drawn over multiple time points (0: not on medications, 1: down-regulation phase of an IVF cycle (oral contraceptives or lupron), 2: IVF stimulation day five, 3: day of hCG trigger, and 4: day of pregnancy test) during infertility treatments were assessed for GnRHR-AAbs. The de-identified samples were screened by ELISA for GnRHR-AAbs using a synthetic 28-mer peptide (LifeTein, Somerset, NJ) from the ECL2 of human GnRHR as coating antigen. Optical density (OD) values were read at 405 nm at 60 minutes. Covariates evaluated include age, body mass index (BMI), anti-Mullerian hormone (AMH) level, antral follicle count (AFC), IVF protocol (GnRH antagonist or agonist), estradiol level, and hormonal down-regulation during IVF preparation. Statistical analyses were performed using generalized estimating equations within a generalized linear modeling framework to account for the repeated measures within each patient. AAb levels did not differ significantly by patient age (range 25-40 years; p=0.85) or BMI (range 19.3-41.8; p=0.89). After taking into account inter-patient variation and inter-time point variation, there was an association between GnRHR-AAb levels and estradiol levels (higher AAb level with lower estradiol; p<0.0001). Also, the GnRH antagonist protocol was associated with lower AAb levels (p=0.019). Most inter-patient variation could not be attributed to any of the patient characteristics. However, after taking into account inter-time point variation only, inter-patient variation in AAb levels was partially attributable to an interaction between BMI and AMH (p<0.0001) but not to age (p=0.70) or AFC (p=0.97). There was significant intra-patient variation in AAb levels at both baseline (time point 0, not on meds, p=0.042) and during the down-regulation phase (time point 1, p<0.0001) that could not be attributed to any of the measured covariates. Our initial investigations have shown that most patients in our study with PCOS have activating AAbs to GnRHR compared to ovulatory controls. Our pilot study has demonstrated that there is inter-patient variation of GnRHR-AAb levels on no medications and while in the down-regulation phase in preparation for IVF. Additionally, the fluctuation in AAb levels with estradiol levels in GnRH antagonist protocol would suggest an association between the two clinical time points and potentially a relationship between estradiol and the GnRHR-AAbs.

Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study.

BACKGROUNDIn IVF, Luteal phase support is usually performed using vaginal progesterone. A part of patients using this route reports being uncomfortable with this route. We tried to study whether the rectal route could be an effective alternative and associated with less discomfort.PATIENTS AND METHODSA prospective randomized controlled study. All patient were eligible for IVF treatment for infertility. After oocyte pickup, 186 patients were allocated to one the following protocols for luteal phase support: (i) rectal pessaries group: natural progesterone pessaries administered rectally 200 mg three times a day, (ii) vaginal pessaries group: natural progesterone pessaries administered vaginally 200 mg three times a day), and (iii) vaginal capsules group: natural micronized progesterone capsules administered vaginally 200 mg three times a day. On the day of pregnancy test, patients were asked to fill in a questionnaire conducted by an investigator in order to assess the tolerability and side effects of the LPS treatment taken. The primary endpoint was the occurrence of perineal irritation.RESULTSFifty eight patients were assigned to the rectal pessaries group, 68 patients to the vaginal pessaries group, and 60 patients to the vaginal capsules group. All patients adhered to their allocated treatment. Implantation and clinical pregnancy rates per transfer did not differ between the three groups. Perineal irritation, which was our primary endpoint, was the same for all the three groups (respectively 1.7 % versus 5.9 % versus 11.7%). Regarding the other side effects, more patients experienced constipation and flatulence with the rectal route, whereas more patients reported vaginal discharge in the vaginal capsules group.CONCLUSIONRectal administration for luteal phase support is effective and well accepted alternative to vaginal route.

Luteal phase support post IVF: individualized early stop

While the need for progesterone-based luteal phase support is well documented, the required treatment duration is not well established, and a practitioners' survey showed a wide range of empiric stopping points. It is suggested that an early stop can be based on assessing endogenous luteal activity on the day of pregnancy test. To examine this approach, data were retrospectively collected on 99 patients with positive pregnancy test and high serum concentrations of oestradiol and progesterone (≥1000 pmol/l and ≥110 nmol/l, respectively), whose luteal support was stopped, and compared with those of 85 patients who did not meet the above criteria, and so luteal support was continued until gestational week 9. Both groups were comparable in terms of live birth and miscarriage rates. We conclude that in the face of strong endogenous luteal activity, exogenous support can be stopped on pregnancy test day, without affecting pregnancy outcome. Further research is needed to substantiate this finding.

Thyroid stimulating hormone levels rise after assisted reproductive technology

The goal of this study was to determine whether high E2 levels after controlled ovarian hyperstimulation affect TSH. Patients completing ART cycles between April-October 2010 were eligible for this cohort study. 180 patients were recruited however those with known thyroid disease were excluded. The final analysis included 154 subjects. Blood was collected at each visit during the ART cycle as well as at the pregnancy test. Samples were frozen at -20°C and analyzed together for E2 and TSH using the same assay kit once all patients had completed their cycles. All participants were treated at the McGill University Health Center. A paired t-test was used to study the difference in TSH levels recorded at maximal and minimal Estradiol levels during ovarian stimulation. Multiple regression analysis was then used to determine if factors such as anti-thyroid antibodies and ovarian reserve measures affect this change in TSH. We used multiple imputation methods to account for missing data. As E2 levels rose from low to supra-physiologic levels during treatment, TSH levels also rose significantly. This increase was clinically significant by the time of pregnancy test. The factors that potentially affected the change in TSH were: male factor/tubal factor infertility, type of protocol used as well as the presence of thyroid antibodies. Although TSH increases during ART, this change only becomes clinically significant on the day of pregnancy test. Future studies should examine TSH changes specifically in certain "at-risk" sub-groups such as those with antibodies and known thyroid disease.

Aspirin and heparin as adjuvants during IVF do not improve live birth rates in unexplained implantation failure

This study tested the hypothesis that using aspirin and/or heparin as adjuvants in IVF improves the treatment outcome. This retrospective cohort–control study recruited 234 consecutive subjects aged ⩽44years who had previously had one or more unsuccessful IVF cycle. All underwent IVF using conventional protocols. The study group received aspirin and/or heparin post embryo transfer until the day of pregnancy test or until 12weeks of pregnancy. The control group did not receive adjuvant treatment. The outcome measures were live birth, clinical pregnancy and miscarriage rates. The outcomes were compared by chi-squared test and relative-risk analysis. Analysis was performed in 206 subjects. There was no statistically significant difference in the live birth rate (35.0%, 36/103 versus 47.6%, 49/103), clinical pregnancy rate (40.8%, 42/103 versus 53.4%, 55/103) and miscarriage rate (14.3%, 6/42 versus 10.9%, 6/55) between the study group and the control group. The data in this study show that low-dose aspirin and/or heparin as adjuvant therapies during IVF do not improve live birth rates in an unselected group of subfertile women who have previously had one or more unexplained implantation failure following IVF.This retrospective study examined whether using aspirin and/or heparin during IVF treatment improves the treatment outcomes. A total of 234 women aged ⩽44years who had previously undergone at least one unsuccessful IVF cycle were recruited into the study. All women underwent IVF treatment. The study group received aspirin and/or heparin from the day of embryo transfer until the day of the pregnancy test or until 12weeks of pregnancy, if pregnant. The control group did not receive aspirin and/or heparin. There were no differences in the live birth rates (35%, 36/103 versus 48%, 49/103), clinical pregnancy rates (41%, 42/103 versus 53%, 55/103) and miscarriage rates (14.3%, 6/42 versus 10.9%, 6/55) between the study group and the control group. The data in this study show that low-dose aspirin and/or heparin treatment during IVF does not improve the live birth rate or reduce the miscarriage rate in women who have had previous unsuccessful IVF treatment and whose immunological status is not known.

A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection

SUMMARY QUESTION: Is vaginal progesterone gel equivalent to vaginal micronized progesterone tablets concerning ongoing pregnancy rate and superior concerning patient convenience when used for luteal support after IVF/ICSI? Equivalence of treatments in terms of ongoing live intrauterine pregnancy rate has not been demonstrated; the 95% confidence interval (CI) for the difference in ongoing pregnancy rate (-8.2 to 0.1%) did not lie entirely within the pre-specified equivalence interval -7 to 7%. No significant differences in clinical pregnancy rates have been observed between vaginal progesterone gel and other vaginal progesterone products in earlier studies. However, all previous studies included a limited number of patients. This was a randomized, multicentre, controlled, assessor-blinded equivalence trial in 18 fertility centres in Denmark and Sweden between March 2006 and January 2010. A web-based randomization program was used with concealed allocation of patients. Patients were randomized to one of two groups: vaginal progesterone gel or vaginal micronized progesterone tablets. There was no blinding of patients. A total of 2057 women ≤ 40 years of age were included and down-regulated, using the long agonist protocol and rFSH for stimulation. Luteal support was given for 19 days after embryo transfer or until a negative pregnancy test Day 14 after embryo transfer. Patient convenience was assessed using questionnaires to be filled in 14 days after embryo transfer, before pregnancy test. Ongoing intrauterine pregnancy rates were 299/991 (30.2%) (95% CI 27.3-33.0%) in the progesterone gel group and 324/992 (32.7%) (29.7-35.6%) in the micronized progesterone tablet group. The difference in ongoing pregnancy rates between the groups was -4.1% (-8.2 to 0.1%) and the difference in live birth rates was -3.4% (-7.4 to 0.7%), both calculated after correction for significant confounders. Patient convenience and ease of use (1 = very convenient, 10 = very inconvenient) was in favour of progesterone gel, as the overall score was 2.9 (2.7-3.0) for progesterone gel and 4.8 (4.7-5.0; P < 0.0001) for micronized progesterone tablets. This large equivalence trial shows that, even though equality could not be demonstrated, there is no substantial difference in ongoing pregnancy rate between vaginal progesterone gel and vaginal micronized progesterone tablets. It also shows that progesterone gel is considered more convenient by the patients. Blinding of patients was not possible in this study, but since the outcome (pregnancy) is robust, blinding would have been unlikely to affect the results. Unfortunately, owing to an error in the randomization, the intended age distribution allocated older women to the micronized progesterone tablet group. In the analysis of results, adjustments were made for age and number of embryos transferred. The results can be generalized to other women ≥ 18 and ≤ 40 years of age undergoing IVF/ICSI who have regular menstrual cycles (25-35 days), both ovaries present and no more than two previous failed IVF attempts. Merck Serono supported the study but had no influence on the design of the study and was not involved in the analysis of the results or preparation of the manuscript. The trial was issued with the EudraCT number 2005-001248-22 with the Protocol code number 95576471.

GnRH agonist ovulation trigger and hCG-based, progesterone-free luteal support: a proof of concept study

It is now well established that a GnRH agonist (GnRHa) ovulation trigger completely prevents ovarian hyperstimulation syndrome. However, early studies, using conventional luteal support, showed inferior clinical results following a GnRHa trigger compared with a conventional hCG trigger in normal responder IVF patients. We here present a novel approach for luteal support after a GnRHa trigger. METHODS Normal responder patients who failed at least one previous IVF attempt, during which a conventional hCG trigger was used, were consecutively enrolled in the study. A GnRH antagonist-based ovarian stimulation protocol was used in combination with a GnRHa trigger (Triptorelin 0.2 mg). The luteal phase was supported with a total of two boluses of 1500 IU hCG: on the day of oocyte retrieval and 4 days later. Neither progesterone nor estradiol was administered for luteal support. The mean age was 33.8 years. The mean (± SD) numbers of oocytes and fertilized oocytes were 6.7 (± 2.5) and 3.6 (± 1.7), respectively. All 15 patients had embryo transfers and 11 patients conceived. On the day of pregnancy test (14 days after retrieval), the mean serum E(2) and progesterone levels were 6607 (± 3789) and 182 (± 50) nmol/l, respectively. Of the pregnancies, seven are ongoing, while four ended as miscarriages. These preliminary results suggest that two boluses of 1500 IU hCG revert the luteolysis after a GnRHa trigger in the normo-responder patient. Importantly, no additional luteal support is needed. The novel concept combines the potential advantages of a physiological dual trigger (LH and FSH) with a simple, patient friendly, luteal support.

Medical Waiting Periods: Imminence, Emotions and Coping

The diagnosis and treatment of various medical conditions requires patients to wait for results that are potentially threatening to their wellbeing (e.g., breast biopsy results, pregnancy test results after fertility treatment and genetic screening outcomes). Little research has been carried out to document the psychological processes that unfold during such waiting periods. The aim of the present study was to document the course of anxiety, depression, positive affect and coping during the waiting period before a pregnancy test result in fertility treatment. Using a daily record-keeping chart designed for fertility treatment, 61 women undergoing IVF were monitored daily for emotional reactions (e.g., anxiety, depression and positive affect) and coping during 7 days of active treatment (stimulation), 7 days of waiting to find out whether a pregnancy was achieved (waiting) and 4 days of reacting to the pregnancy test results (outcome). The stimulation stage of treatment was characterized by positive affect with a lesser degree of anxiety, whereas the predominant emotions in the waiting stage were a combination of positive affect and anxiety symptoms versus depression. From the pregnancy test day onwards, the predominant emotion was depression. There was a significant increase in coping activity between the stimulation and waiting stages, with variable effects across coping strategies. It was concluded that whilst medical waiting periods have a clearly defined emotional trajectory, the coping pattern is less differentiated. This may explain why waiting for medical test results is so demanding. Healthcare professionals can assist their patients by facilitating coping strategies that better fit the demands of the waiting period and by offering support once outcomes are known.

Luteal support in reproduction: when, what and how?

Luteal phase support (LPS) is an integral part of the IVF cycles treated by gonadotropin-releasing hormone analogues. There is a worldwide controversy concerning the type of hormones used for LPS, its dose, duration, when to start and when to stop. This review will cover original as well as recent data on this topic. There is a consensus in the literature among IVF centers that LPS is necessary for IVF cycles. Human chorionic gonadotropin is less commonly used than progesterone for LPS because of ovarian hyperstimulation syndrome risk. Several studies suggested that intramuscular progesterone is superior to vaginal progesterone for LPS; however, the majority of centers use vaginal progesterone to avoid side effects of intramuscular injection. There is no difference in pregnancy rate whether LPS is started on day of human chorionic gonadotropin, oocyte retrieval or embryo transfer. There is a strong evidence that LPS should be stopped either on the day of pregnancy test or the first ultrasound (6-7 weeks pregnancy). There is no evidence that addition of estrogen will improve pregnancy rate. Progesterone is the preferred option for LPS. It should start within 2 days from triggering ovulation and should end on day of beta human chorionic gonadotropin or the day of the first ultrasound (6-7 weeks pregnancy).

Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment

Doppler assessment of uterine artery blood flow for the prediction of pregnancy after assisted reproduction treatment