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The objective was to evaluate the outcomes of in vitro maturation (IVM) cycles using gonadotropin releasing hormone agonist (GnRH-ag) triggering. A retrospective cohort of IVM cycles from January 2...

The increased use of vitrified blastocysts has encouraged the development of various criteria for selecting the embryo most likely to implant. Post-thaw assessment methods and timetables vary among investigators. We investigated the predictive value of well-defined measurements of human blastocyst re-expansion, following a fixed incubation period. Post-thaw measurements were taken exactly at 0 and 120 ± 15 min. Minimum and maximum cross-sectional axes were measured. Three groups were defined: Group 1: embryos that continued to shrink by 10 µm or more; group 2: embryos that ranged from −9 to +9 µm; and group 3: re-expansion of 10 µm or more. Patient and morphokinetic data were collected and integrated into the analysis. A total of 115 cases were included. The clinical pregnancy rate for group 1 was 18.9%; group 2, 27%; and group 3, 51.2% (p = 0.007). Pre-thaw morphologic grading and morphokinetic scores of the study groups did not reveal differences. p-values were 0.17 for the pre-thaw morphologic score, 0.54 for KID3, and 0.37 for KID5. The patients’ demographic and clinical data were similar. The clinical pregnancy rate correlated with the degree of thawed blastocyst re-expansion measured 2 h after incubation. This standardized measure is suggested as a tool to predict the potential of treatment success before embryo transfer.

PURPOSE: Does thawing cleavage embryos and culturing them for transfer as blastocysts improve pregnancy and perinatal outcomes compared to transferring thawed blastocysts? METHODS: Retrospective, observational cohort study performed at two assisted reproductive technology centers, 2014 to 2020. A total of 450 patients with 463 thawed embryo transfer cycles were divided into 2 groups according to the embryonic developmental stage at cryopreservation and transfer: 231 thawed blastocysts (day 5 group) and 232 thawed cleavage embryos that were cultured for 2 days and transferred as blastocysts (day 3–5 group). The two groups were compared for demographics, routine parameters of IVF treatment, pregnancy rates, and perinatal outcomes. RESULTS: Multivariable logistic regression analysis for ongoing pregnancy and delivery demonstrated that the day 3–5 group had a greater likelihood of achieving ongoing pregnancy and delivery compared to the day 5 group (OR 1.58, 95%CI 1.062–2.361, p = 0.024). Perinatal outcomes were comparable between the three groups. CONCLUSION: Our results support culturing post-thaw cleavage embryos for 2 days and transferring them as blastocysts to increase chances of ongoing pregnancy and delivery.

Research question What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF? Design A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1–10 Visual Analogue Scale (VAS, referred to as the ‘Stress Scale'. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed. Results Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 μg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 μg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 μg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004). Conclusion It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.

Telomeres are a specific base sequence of DNA, responsible for chromosome stability and DNA protection. We aimed to investigate the association between telomere systems and IVF outcomes according to patients' BMI. For all telomere characteristics, there was a distinct trend towards shorter telomeres and activation of telomere shortening compensatory mechanisms in the BMI group >25 kg/m2, reaching statistical significance for senescence only (r = 0.7, p value

Aim: To evaluate the number of oocytes retrieved as a criterion - when to use a “freeze-all” or low-dose “rescue human chorionic gonadotropin (hCG)” strategy. Methods: A retrospective study. Instead of the classic hCG trigger, an E2 level of ≥3,000 pg/mL was used to trigger ovulation with GnRH agonist. The decision whether to “freeze all” or perform fresh embryo transfer (ET) with a bolus of hCG was made based on a maximum number of 20 oocytes retrieved. Beyond this cut off, a “freeze-all” strategy was implemented. Below this cut-off value, a fresh ET using a single bolus of 62.5 µg hCG on day 3 following oocyte pick-up was performed. The main outcome measures were clinical pregnancy rates and ovarian hyperstimulation syndrome (OHSS). Results: E2 and progesterone levels increased after the rescue hCG bolus administration (E2 from 643.4 ± 311.1 to 1,086.1 ± 574.7 pg/mL, p = 0.003 and progesterone from 13.1 ± 4.8 to 39.2 ± 28.7 ng/mL, p < 0.0001). The clinical pregnancy rates were 25% in the freeze-all group and 32% in the rescue hCG group (p = 0.57). OHSS was not reported in either group. Conclusions: Both strategies seem to be efficacious and safe. An upper limit of 20 retrieved oocytes appears to be safe for applying a rescue hCG strategy.

This prospective cohort pilot study investigated the physiology of C-reactive protein (CRP) during in vitro fertilization (IVF) cycles and its effect on outcomes in women with and without obesity. The study was conducted from April to August 2014, in the IVF Unit of a university-affiliated hospital. Women aged 18-42 years were enrolled. Those with chronic inflammatory diseases or acute illness were excluded. A total of 31 patients were included: 17 with BMI < 30 kg/m2 and 14 with BMI ≥ 30 kg/m2. Serum CRP levels were measured: (i) before starting ovarian stimulation; (ii) on the day of β-HCG administration; and (iii) on day of ovum pick-up (OPU), in both serum and follicular fluid. Serum CRP levels were significantly higher in women with obesity at all time points. For the entire cohort, a positive correlation was found between basal oestradiol (E2) and basal CRP (r = 0.71, p < 0.05). A specific pattern of CRP levels was not detected during the IVF cycle. High serum CRP levels on OPU day had a negative effect on embryo quality (p = 0.056). CRP ≥ 0.5 mg/dL was associated with lower quality embryos (2.6 ± 0.3 vs. 3.3 ± 0.3; p = 0.04). High serum CRP level on OPU day negatively affects embryo quality.

Research question What are the safety and feasibility of repeated subcutaneous doses of gonadotrophin-releasing hormone (GnRH) agonist for luteal support in IVF cycles triggered by a GnRH agonist? Design In this prospective trial, patients exhibiting oestradiol concentrations of over 2500 pg/ml after use of a GnRH agonist for triggering ovulation were initially randomized to GnRH agonist luteal support (0.1 mg subcutaneously every other day, starting on day 3 after embryo transfer) or to a control group supported by 80 µg of recombinant human chorionic gonadotrophin (HCG) on day 3 after embryo transfer. All patients underwent a day 5 blastocyst transfer. Randomization to the HCG luteal support was stopped owing to two cases of ovarian hyperstimulation syndrome (OHSS) and the study was continued solely with GnRH agonist luteal support. Results The study included 39 women in the repeated GnRH agonist luteal support group and seven in the HCG micro dose group. There were no cases of OHSS among patients supported by a GnRH agonist, and no other adverse events were recorded. There were no cases of bleeding before the pregnancy test, and hence no cases of an insufficient luteal phase. A clinical pregnancy rate of 43.6% was achieved with GnRH agonist luteal support. Hormone dynamics during the stimulation cycle reflected rising LH and progesterone concentrations after the introduction of GnRH agonist support. Conclusions Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.

Multifetal pregnancy reduction (MPR) is an accepted method of reducing complications of triplet pregnancies and higher-order multifetal pregnancies. Eighty-three pregnancies that underwent early (68 weeks) transvaginal MPR were compared with 125 pregnancies that underwent late (11-14 weeks) transabdominal MPR. Rates of pregnancy loss, preterm delivery, gestational diabetes and hypertensive disorders were similar among both groups. Early MPR was associated with a lower risk for small for gestational age newborns (6.5% versus 19.2%; P = 0.034; OR 0.32; 95% CI 0.11 to 0.92) and a higher risk for single-fetus loss (6% versus 0.8%; P = 0.041; OR 10.58; 95% CI 1.1 to 101.94). Preterm delivery rates seemed to be similar between the two groups. In MPR from triplets, an apparent benefit was observed for early MPR in preterm deliveries before 37 weeks, whereas, in MPR from high-order pregnancies, a benefit was observed for late MPR in deliveries before 32 weeks. Perinatal outcomes of twin pregnancies after early and late MPR seem to be grossly similar. Optimal timing for multifetal reduction depends on other factors, namely, the selectivity of the procedure and patient's preference.

Objective Investigate a novel office hysteroscopic tubal catheterization therapeutic method for proximal tubal occlusion. Study design Prospective cohort study in a tertiary referral center. We evaluated the procedure on a group of 27 patients that were referred to our unit for proximal tubal occlusion demonstrated by hysterosalpingography, 9 (33.3%) of them with primary infertility and 18 of them (66.6%) with secondary infertility. The intervention included the usage of the modified Novy cornual cannulation set which was inserted through a 5F working cannel during an office operative hysteroscopy, followed by fallopian tube irrigation with saline-air mixture under ultrasonographic imaging. Results Our series revealed no complication during or after the procedure; anesthesia was not required. One patient lost from follow-up. Of the remaining 26, 10 patients (38.4%) conceived either spontaneously or with treatment by clomiphene or gonadotropine associated with intrauterine insemination. The median time to conception was 5 months (range 4–17). Conclusion We therefore concluded that office hysteroscopic tubal catheterization is a simple (without anesthesia required) option for the treatment of patients suffering from proximal tubal occlusion. Fertility outcomes in our series are comparable to other treatments options for tubal catheterization. Therefore, tubal catheterization should not delay the assisted reproducted techniques if indicated but we propose to include it in a global integrated approach.

The purpose is to provide a summary of the effects of cigarette smoking on steroid hormone metabolism and how it affects female fertility.Components of tobacco smoke such as polycyclic aromatic hydrocarbons lead to transcriptional upregulation of a number of genes, including members of the cytochrome P450 (CYP) family, in particular CYP1B1 and CYP1A1. In humans, CYP1A1 and CYP1A2 are the primary enzymes catalyzing the 2-hydroxylation of estradiol. This pathway shunts available estrogen away from the more estrogenically potent 16α-hydroxylation to the production of catechol estrogens, mainly 2 and 4 hydroxyestradiol.Smoking has multiple effects on hormone secretion and metabolism. These effects are mainly mediated by the pharmacological action of tobacco alkaloids (nicotine and its metabolite cotinine). A strong body of evidence indicates that the negative effects of cigarette smoking on fertility compromises nearly every system involved in the reproductive process.

Telomeres are a specific base sequence of DNA, responsible for chromosome stability and DNA protection. We aimed to investigate the association between telomere systems and IVF outcomes according to patients' BMI. For all telomere characteristics, there was a distinct trend towards shorter telomeres and activation of telomere shortening compensatory mechanisms in the BMI group25

Research question What pregnancy rates are achieved after transfer of cryopreserved double slow-frozen embryos in IVF cycles? Patients in whom surplus thawed cleaved embryos (day 2 or 3) were grown to the blastocyst stage, re-frozen and then re-thawed for transfer (double freezing) were included. Design Data were collected on all patients who had undergone the above procedure at the IVF unit of Assuta Ramat Hachayal Hospital, Tel Aviv, during a 7-year period. For each patient in the study group, the two-consecutive, matched-by-age patients treated with frozen–thawed single blastocyst transfer were selected to form a 2:1 ratio control group. All embryos were frozen using the slow freeze protocol. Results A total of 54 patients had 70 embryos that were re-frozen at the blastocyst stage. Twenty-eight of these blastocysts were thawed and 27 underwent transfer to 25 patients. A single embryo was transferred to 23 patients and two embryos were transferred to two patients. The survival rate of the second thawing was 96.4% (27/28). Clinical pregnancy rate was 16% (4/25) and implantation rate was 14.8% (4/27). In the study group, pregnancies were achieved in 22 out of the 25 patients using IVF treatment, indicating good receptivity of the uterus. In the control group, the implantation/pregnancy rates were significantly higher (44.2% [23/52]; P Conclusion The transfer of twice slow-frozen and thawed embryos does not seem to be a beneficial approach in the planned management of cryopreserved surplus embryos owing to the low pregnancy rate achieved after transfer of the re-frozen blastocyst embryos.

To evaluate whether high LH/FSH ratio has a clinical impact on patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) with GnRH-agonist/antagonist protocols or in vitro maturation (IVM) treatments.We retrospectively reviewed all PCOS patients with day 3 LH/FSH ratio ≥1.5 who underwent IVF or IVM. The main outcomes measures were embryo quality and pregnancy rate.A total of 75 cycles were included. Among these, 44 patients underwent long agonist protocol, 16 antagonist protocol and 15 IVM. Age, basal LH and FSH levels, as well as duration of infertility were comparable for all groups. The LH level on the day of hCG administration was significantly lower in the antagonist group (0.9 IU/ml) compared to the long agonist group (1.4 IU/ml, p = 0.01). There was no difference in pregnancy rates among the groups: 27.2 % in the long agonist group, 37.5 % in the antagonist group and 26.6 % among the IVM patients.High LH/FSH ratio had no adverse effect on pregnancy rates in all three treatment modes.

Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift.

Objective: To evaluate the effect of dilation and curettage (D&C) and misoprostol as treatments for spontaneous miscarriage (SM) on in vitro fertilization (IVF) parameters in the subsequent IVF cycle.Design: Multicenter, retrospective, cohort study. Women treated for SM after IVF treatment with D&C or misoprostol and underwent a subsequent IVF cycle was included. The main outcome measures were ovarian response, endometrial thickness and pregnancy rate in the subsequent IVF cycle after MA.Results: Among 73 patients with miscarriage, 41 had D&C and 32 were given misoprostol. Baseline serum follicle stimulating hormone (FSH) levels and ovarian responses before and after treatment of miscarriage were comparable. No significant differences were observed between the D&C and the misoprostol groups in basal FSH levels, endometrial thickness and parameters of ovarian response in the subsequent IVF cycle.Conclusion: D&C and misoprostol are both effective treatments for IVF patients with miscarriage, without...

Background IVF cycles which result in only one good quality embryo, and a second poor quality embryo present a dilemma when the decision involves transferring two embryos. The aim of this study was to evaluate whether a poor quality embryo has a negative effect on a good quality embryo when transferred along with a good quality embryo. Methods We retrospectively evaluated in vitro fertilization (IVF) cycles involving single embryo transfers (SET) and double embryo transfers (DET). Embryo quality was divided into poor “P” and good “G” quality. The main outcome measures were: live birth, implantation rate, miscarriage rate, clinical pregnancy rate and multiple pregnancy ratio. Results Six hundred three women were included. The study group consisted of 180 (29.9%) patients who had a double embryo transfer (DET) with one poor quality embryo and one good quality embryo (P + G). Control 1 group included 303 (50.2%) patients who had DET with two good quality embryos (G + G), and control 2 group consisted of 120 (19.9%) patients who had a single embryo transfer (SET) with one good quality embryo (G). Live birth rates were not significantly different when compared between study groups: 30.8% in the SET group (G), 27.2% in the (G + P) group and 33.7% in the (G + G) group. The SET group had the highest implantation rate (33.9%) compared to the DET groups (21.8% (G + P), 25.4% (G + G)) (P =0.022). The clinical pregnancy rate was 33.3% in the SET group (G), 33.3% in the (G + P) group, and 39.3% in the (G + G) group (P =0.39). The miscarriage rate was comparable in all groups. Conclusion A poor quality embryo does not negatively affect a good quality embryo, when transferred together in a double embryo transfer. Electronic supplementary material The online version of this article (doi:10.1186/s13048-016-0297-9) contains supplementary material, which is available to authorized users.

The aim of our study was to evaluate time lapse microscopy (TLM) as a selection tool for single-embryo transfer (SET) on day 5, blastocyst stage. An observational cohort study was conducted. Patients who had SET were compared to patients who had double embryo transfer (DET). A total of 108 patients were included in analysis, 83 had SET, and 25 underwent DET. Embryos were incubated and evaluated using TLM. The pregnancy rates were similar between the groups (42.2% in SET and 48.0% in DET). However, the multiple pregnancy rate was significantly higher in the DET group compared to the SET group (41.7% versus 2.9%, respectively; p

background: Hyper-activated motility (HAM) is part of the sperm capacitation process, which is necessary for fertilization. In this study, we investigated the effect of visible light on sperm motility and hyperactivation and evaluated pathways mediating these effects. methods: Human sperm (1 × 10 7 cells/ml) in capacitation media were irradiated for 3 min with 40 mW/cm 2 visible light (400–800 nm with maximum energy at 600 nm). Sperm motility was assessed and analyzed by computer-assisted sperm analysis. The involvement of sperm capacitation factors was investigated as follows. The generation of reactive oxygen species (ROS) was measured using 20,70dichlorofluorescein diacetate. Protein kinase A (PKA) and sarcoma protein kinase (Src) activity were measured using western blot analysis and inhibited using 50 mM H89 and 10 mM PP2, respectively. Soluble adenlyl cyclase was inhibited using 20 mM 2-OH-Estradiol. The intracellular concentration of free Ca 2+ was assessed using the fluorescent calcium indicator, Fluo-4/AM. Sperm DNA fragmentation was determined using the sperm chromatin dispersion test. results: Light irradiation of human sperm caused a significant increase in hyper-HAM but not total motility. The production of ROS and activation of soluble adenylyl cyclase and PKA mediated the effect of light on HAM. Light irradiation also activated Src, and inhibition of Src significantly reduced the effect of light on HAM. Light irradiation caused a rapid increase in intracellular Ca 2+ concentration and the increase in HAM was significantly reduced when voltage-dependent-Ca 2+ -channel activity was blocked or when Ca 2+ -deficient medium was used. conclusions: Light irradiation of human sperm for a short time causes a significant increase in HAM in a mechanism mediated by ROS production, activation of PKA, Src and Ca 2+ influx.

The aim of this study was to find discriminatory parameters, based on sperm characteristics on the day of ovum pickup, that can help guide the decision to perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination during the same cycle. A total of 112 cycles were analysed. In 62 cycles, fertilisation was obtained with both ICSI and IVF, and in 50 cycles, fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated after the preparation process. The mean initial total motile sperm count (TMSC) was 66.3 × 10(6) ± 47.5 in the group that underwent both methods and 23.1 × 10(6) ± 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the mean post-wash TMSC was 4.4 × 10(6) ± 3.4 and 1.06 × 10(6) ± 0.9 respectively (P < 0.05). A cutoff of 1.5 × 10(6) or fewer sperm after preparation as an indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re-evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5 million TMSC after wash should be considered an indication for ICSI fertilisation.

To determine factors that affect the success rate of GnRH antagonist protocol in in vitro fertilization (IVF) treatment.Retrospective cohort study.Patients who underwent IVF cycle with their first GnRH antagonist protocol.Antagonist protocol during IVF treatment. The main outcome measurements were; Number of retrieved oocytes, embryo quality and pregnancy rate.Gravidity was negatively correlated with number of eggs (p = 0.017), while total follicle number ≥15 (p = 0.044) and E(2) on day of human chorionic gonadotropin (HCG) (p = 0.000) had a positive correlation with number of eggs. Maximum follicle size at HCG administration showed a trend toward an inverse correlation (p = 0.053). Addition of LH to drug stimulation was negatively correlated with number of eggs in comparison to rFSH only (p = 0.013 and 0.0000, respectively). Age and number of frozen eggs were negatively correlated with successful pregnancy (p = 0.025 and 0.004, respectively), while embryo quality, gravidity and number of embryos were positive (p = 0.011 and 0.014, respectively).Controlled parameters like timing of antagonist start, duration of antagonist and the optimal leading follicle diameter for HCG triggering had no effect on treatment outcomes.

The objective of this study was to assess the safety of induction of ovulation and oocyte retrieval in patients at risk of thrombosis, necessitating treatment with anticoagulants. Twenty-four patients considered as high risk for a thromboembolic event underwent 73 IVF cycles and 68 oocyte retrieval procedures, and were treated concomitantly with anticoagulation therapy (low molecular weight heparin; LMWH). A subgroup of five patients considered at especially high risk for thrombosis was isolated. These patients were prepared for oocyte retrieval using a controlled spontaneous cycle. All these patients were programmed exclusively for surrogacy. Nineteen women underwent 49 cycles of ovulation induction with gonadotrophins. The average peak oestradiol concentration was 1791 +/- 1420 pg/ml with an average of 13.5 +/- 8.4 oocytes retrieved in each cycle. The five patients from the very high risk group underwent 24 cycles: the average peak oestradiol concentration was 163 +/- 98 pg/ml. In 18, an egg was retrieved and in 14, fertilization was achieved. No bleeding or thromboembolic complications were noted during treatment of both groups of patients. It is concluded that during induction of ovulation in patients at risk for thrombosis, the introduction of LMWH as a cycle protective treatment was not associated with any medical complication. The use of a controlled spontaneous cycle with LMWH is suggested in very high risk patients.

Objective: This study was designed to evaluate the role of zygote intrafallopian transfer (ZIFT) procedure in patients with repeated failure of implantation. Study Design: A total of 141 ZIFT cycles of 132 women and 145 embryo transfer (ET) cycles of 97 women in whom five or more embryos were transferred were included in this study. Transcervical uterine embryo transfer and ZIFT cycle outcome in patients with five or more previous implantation failure were compared. Embryos were transferred by laparoscopy into the fallopian tube 24–27 h following oocytes retrieval in the ZIFT group. In the ET group, embryos were transferred transcervically on the third day following oocytes retrieval. Results: The mean age was 34 ± 4.9 and 34.9 ± 5.0 years in ZIFT and ET group, respectively. No difference was determined between the two groups regarding the basal FSH, E2 value on the day of HCG injection and the number of oocytes retrieved or fertilized. The implantation rate was 6.5% versus 7.2%, clinical pregnancy rate was 22.7% versus 24.8% and live birth rate was 21.2% versus 16.5% in ZIFT and ET groups, respectively. Conclusions: Implementation of ZIFT procedure in patients with repeated implantation failure is not superior to transcervical uterine embryo transfer.

Assisted reproductive technologies (ART) have increased both the number of pregnancies in women beyond the age of 35 and the incidence of multiple pregnancies. Various methods of screening for Down syndrome (DS) were introduced in clinical practice during the last two decades, and specific problems were encountered when they were applied for twin pregnancies. The current review aims to explore the problematic issue of prenatal DS screening in ART twins. Overall, more women with twin pregnancies (mainly those who conceived via assisted reproduction) are found to be false positive for DS. This is because mid-trimester maternal serum screening is associated with a higher false-positive rate secondary to changes in the feto-placental endocrinologic metabolism, reflected mainly in high human chorionic gonadotrophin (hCG) levels in the ART pregnancies. First-trimester nuchal translucency (NT) measurement in twin pregnancies is not affected by the problems encountered in serum screening. This sonographic screening approach enables a fetus-specific identification of those fetuses at high risk of DS and is associated with a lower false-positive rate than mid-trimester serum screening. DS screening in ART twins presents several challenges in determining the most appropriate screening test modality. Whether there is any significant benefit of adding first-trimester biochemistry or nasal bone scanning in screening ART-conceived twins awaits further investigation.

The objective of the study was to evaluate, clinically and sonographically, the time required for the progestative effect of the levonorgestrel-releasing intrauterine system (IUS, Mirena) to be manifested. Doppler flow of the cervical branch and spiral artery of the uterine artery, as well as the endometrial width (up to day 10 of the cycle), were evaluated in 36 women carrying levonorgestrel-releasing IUS 1-2 months after insertion of the device compared to 4-6 months after insertion. The rate of intermenstrual bleeding was reduced from 44% during the first 2 months, to only 8% of women after 4-6 months of use. Complete cessation of menstrual bleeding occurred in 5% after 2 months and in 66% after 4-6 months following insertion. While there was no change in the Doppler flow in the cervical branch of the uterine artery between both groups, there was a significant reduction in the subendometrial flow in the spiral artery. This observation was reinforced by the demonstration of significant reduction in endometrial thickness in the following 4 months of use. The present study has demonstrated that the local progestative effect of the levonorgestrel-releasing IUS on the endometrium is already manifested within a period of 3 months and over after insertion.

Objectives Alteration of mid-gestation serum markers in assisted-conception pregnancies is believed to be attributable to ovarian superovulation treatment modalities. We compared alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3) in two groups of unstimulated assisted-conception pregnancies, that is, own-oocyte frozen embryos (own-FET) versus oocyte-donated (OD) embryos. Methods Forty-three OD-conceived and 31 own-FET-conceived singleton parturient women (aged 29 ± 4 years and 31 ± 4 years respectively, P < 0.05) were followed from embryo transfer throughout pregnancy. Results The daily pattern of first-trimester serum β-hCG was similar in both groups. The OD group had only significantly increased AFP concentrations compared to the own-FET group (1.38 vs 0.99 median MoM respectively, P = 0.002). Although there were no chromosomal abnormalities and no fetal or neonatal deaths in either group, 12% OD women and 6.5% own-FET women were found screen-positive. Eight OD women and 11 FET women had an adverse obstetric outcome (P = NS). Conclusion OD embryos are a unique clinical model for evaluating the uterine compartment and its contribution to mid-gestation serum marker secretion. Copyright © 2003 John Wiley & Sons, Ltd.

To evaluate if monitoring patients by ultrasound (US) only during in vitro fertilization (IVF) treatment is safe.Randomized prospective study.Patients undergoing their first IVF treatment were randomized into two groups. The ultrasound only group (study group) was monitored by US for follicle size and endometrial thickness without blood tests. In this group, only one blood test was taken before human chorionic gonadotropin (hCG) injection, to ensure a safe level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit.Clinical pregnancy rate.No differences were found between the groups in the parameters of IVF treatment, induction days, number of ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy rate was not statistically different between the groups, 57.5% vs. 40.0%, respectively (p = 0.25). No OHSS cases were found among the study or control groups.Ultrasound as a single monitoring tool for IVF cycles is reliable, safe, patient friendly, and reduces treatment expenses. In an era of cost effectiveness awareness, this regimen should be considered for routine management in IVF programs.

The present study aimed to determine a reliable tool to estimate the interval time to delivery in assisted conception twin pregnancies. Mid-gestation cervical length was prospectively measured using transvaginal sonography (TVS) during routine antenatal care. Fifty-seven of 101 suitable women were longitudinally followed and two TVS measurements of their cervical length were obtained, first at approximately 24 weeks gestation and then at approximately 27 weeks gestation. The mean cervical length decreased from 37 ± 12mm at first measurement to 34 ± 11mm at the second one. A linear regression model was found between the time interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p < 0.001) assessments and the week of delivery. The current data confirm that the length of the preserved segment of the cervix is an important indicator of its competence. A simple equation using the cervical length (mm) divided by 3 can predict mid gestation scan-to-delivery interval in twin gestation.

Objectives To compare the outcome of multifetal pregnancy reduction from triplets to twins performed either early (at 11–12 weeks' gestation) or late (at 13–14 weeks). Methods Ninety-five high-order pregnancies following assisted conception were studied. Transabdominal sonographically guided multifetal pregnancy reduction was performed early in 46 women, while 49 women first underwent a sonographic fetal anomaly scan before undergoing selective reduction. Results Sonographic screening led to selective termination of a specific fetus in nine cases due to increased nuchal translucency and relative intrauterine growth restriction in three cases each, and meningomyelocele, abdominal cyst and cystic hygroma in one case each. In the early reduction group a diagnosis of hypoplastic left heart in the two remaining twins was subsequently made, and one pair of twins suffers from cerebral palsy. The rate of pregnancy loss was not statistically different between the early (4.3%; 2/46) and late (4.0%; 2/49) termination groups. The birth weight and gestational age at birth were not statistically different between the early (n = 85) and late (n = 94) groups (2110 ± 580 vs. 2140 ± 490 g, and 35.8 ± 3.0 vs. 35.7 ± 3.5 weeks). Similarly there was no statistically significant difference between early and late groups in the incidence of very premature (24–32 weeks; 9.3 vs. 8.3%) and premature (33–36 weeks; 46.5 vs. 47.9%) births. Conclusions Early second-trimester multifetal pregnancy reduction from triplets to twins may allow more selective termination of abnormal fetuses without an adverse effect on the outcome of pregnancy. However, further studies are needed in order to confirm our observations in a larger series. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

This prospective study was designed to examine the feasibility of natural cycle in vitro fertilization (IVF) in poor responders, and the clinical factors that may predict successful outcome. Twenty-two poor responders underwent IVF treatment with 44 unstimulated cycles. The results of the natural cycles were compared with those of the 55 low-response stimulated cycles of these patients during the 12 months prior to the study. Eighteen (82%) patients had at least one oocyte retrieved, while nine (41%) had at least one cycle with embryo transfer. Two (9%) patients each gave birth to a healthy term baby. These results are comparable with those of the stimulated cycles. Serum early follicular follicle stimulating hormone (FSH) level was found to be the only reliable predictor of oocyte recovery and overall outcome in each specific natural cycle. However, because of great variability in basal FSH levels among different cycles of the same patient, this is not a reliable predictor of outcome in future cycles. We conclude that poor responders are a unique group of patients who may benefit from natural-cycle IVF treatment.

The aim of this prospective randomized study was to compare the effects of two gonadotrophin-releasing hormone (GnRH) agonists, buserelin and triptorelin, on human ovarian follicular steroidogenesis, oocyte fertilization and IVF treatment outcome. Ovulatory, healthy women undergoing IVF were treated either with human menopausal gonadotrophin (HMG) alone or with HMG and one of the two GnRH agonists. Serum and follicular fluid hormonal concentrations and cultures of luteinizing granulosa cells obtained during follicular aspiration were analysed. GnRH agonist treatment significantly affected steroidogenesis both in serum and follicular fluid. In follicular fluid, progesterone and oestradiol concentrations were significantly elevated while testosterone concentrations were significantly lower in the triptorelin group. The ratios of testosterone/progesterone, oestradiol/progesterone but not oestradiol/testosterone concentrations were significantly affected by GnRH agonist administration. Similarly, the steroidogenic activity of luteinizing granulosa cells in vitro was significantly decreased in women treated with GnRH agonists. Women treated with GnRH agonists had significantly more fertilized oocytes and cleaving embryos. The results indicate a marked effect of GnRH agonists on the pattern of ovarian follicular steroidogenesis that cannot be explained solely by changes in gonadotrophin concentrations.

Oocyte donation has become a common treatment modality for a large spectrum of infertility conditions. The purpose of this study was to assess the success rate of a shared egg donation programme, and to define the profile of a successful 'donor-recipient' couple in view of the limitations imposed by the shared programme. The results of all consecutive cycles of egg donation from 1st January 1995 to 31st December 1996 were analysed. A total of 383 donor cycles were matched with 946 recipient cycles; clinical pregnancy rates were 23. 5 and 16.7% respectively. With the exception of endometriosis, which significantly reduced the pregnancy rate in both groups, similar pregnancy rates were obtained in both groups for all the other infertility aetiologies of the donors. The donor's age had no impact on pregnancy rate of the recipient, but pregnancy rate was significantly decreased in donors >35 years. Recipients >50 years had significantly reduced pregnancy rates and those >45 years a significantly increased abortion rate. Recipients with severe male factor infertility, who had intracytoplasmic sperm injection treatment, showed pregnancy rates equivalent to those recipients who had regular in-vitro fertilization. We conclude that in a shared egg donation programme, the recipients' pregnancy rate and outcome are dependent only on the donors' infertility aetiologies and on recipients' ages.

Chronic intake of alcohol in high doses adversely affects almost all body systems, and no other toxic substance deserves more attention in view of the havoc it has wrought. The generally accepted definition of an alcoholic is someone whose habit has produced substantial continuing or recurrent interference with a major area of life, health, interpersonal relationships, or socioeconomic status. The alcoholic is often obese, because of the ingestion of excess calories as alcohol, but undernourished with respect to proteins, essential fatty acids, vitamins, and minerals. As each jigger of whiskey or glass of beer or wine contains over 100 calories, the chronic drinker consumes a large amount of calories as alcohol. The lack of vitamins and other nutrients in alcoholic beverage leads to nutritional deficiencies, and may result in the clinical paradox of an obese patient suffering from malnutrition. Virtually the entire endocrine system is affected by ingestion of chronic high amounts of alcohol. Great strides have been made over the past years in our understanding of both the physiologic and the psychologic effects of alcohol; however, the literature reveals that the majority of reported experimental results evaluating the effects of alcohol on human behavior have been derived from male participants; women essentially have been ignored in the experimental analysis of alcohol effects. Several papers indicate that men and women may react differently to the ingestion of alcohol1; moreover, women react differently to the same amount of alcohol at different periods during the menstrual cycle. Women obtain significantly higher peak blood alcohol levels than do men at the equivalent dose of alcohol. Women tested during the premenstrual phase reach significantly faster absorption rates than do women tested at other phases in the menstrual cycle. 2 One study suggests that women become more intoxicated than do males at the equivalent doses of alcohol, particularly if the women drink during the premenstrual phase.2 These response differences should be considered in future research, and they suggest that sex hormone levels may be related to the behavioral effects of alcohol.

Purpose:Our purpose was to assess the incidence of multiple pregnancies and their obstetric outcome after intracytoplasmic sperm injection. Methods:The study group comprised women who delivered twins or triplets after intracytoplasmic sperm injection and standard in vitro fertilization. The incidence and main perinatal outcome of 140 multiple pregnancies resulting from intracytoplasmic sperm injection or standard in vitro fertilization treatment were analyzed. Results:A total of 60 multiple pregnancies was obtained after intracytoplasmic sperm injection (3.4 ± 1.1 embryos/cycle) and 80 after standard in vitro fertilization (3.3 ± 2.0 embryos/cycle). The incidence of multiple pregnancy, i.e., 22.6 compared to 20.7%, respectively, was calculated. The obstetric outcome of 47 multiple pregnancies after intracytoplasmic sperm injection was 39 twin deliveries at between 27 and 37 weeks of gestation (mean, 36 ± 3.3) and 8 successful triplet deliveries between 26 and 36 weeks of gestation (mean 32.6 ± 2.4). The outcome after regular in vitro fertilization was similar. No major malformations were observed. Conclusions:The results of this study showed that the incidence of multiple pregnancies after intracytoplasmic sperm injection was similar to that after standard, conventional in vitro fertilization. The perinatal outcome did not differ between both groups.

The harmful effects of cigarette smoking are not limited only to those tissues with direct contact with the smoke. Smokers have increased risks of cancer of the esophagus, kidney, and bladder, presumably from swallowed or absorbed cigarette products. Some hormonal effects of smoking, such as acute catecholamine and corticosteroid release, appear to be due to the stimulation of the adrenal medulla or of the hypothalamus, with subsequent adrenocorticotropic hormone secretions. Certain other effects on organs lacking direct smoke contact appear to follow an important pattern; in many ways women who smoke cigarettes behave as though they are relatively estrogen deficient. Such an antiestrogenic effect of smoking would of course lead to an exacerbation of estrogendeficiency problems, such as osteoporosis, but would also have unexpected beneficial effects on diseases caused by estrogen excess, such as endometrial cancer. Furthermore, this antiestrogenic effect of smoking seems to affect male smokers as well, with an increased tendency for ischemic heart disease. We review herein various effects of cigarette smoking on the endocrine system.

Purpose: Our purpose was to evaluate whether the source of spermatozoa influences the results of intracytoplasmic sperm injection (ICSI) treatment in couples with severe malefactor infertility. Methods: A retrospective analysis of 40 cases of ICSI with testicular-retrieved spermatozoa, matched with 40 cases of ICSI with ejaculated spermatozoa, was performed. We included only couples with normoovulatory females younger than 37 years who were matched according to the day of ovum pickup with the patients in the study group. Results: Eighty cycles were analyzed: 40 cycles using testicular spermatozoa and 40 cycles using ejaculated spermatozoa. In 32 (80%) of the 40 ICSI transcutaneous needle aspiration cycles, we obtained enough spermatozoa to inject all the mature oocytes retrieved. In eight (20%) cases there were not enough spermatozoa to inject all the oocytes. Only 76 (54%) of 141 available oocytes were injected in these eight patients. The oocyte fertilization rates were 42% for the study group and 55.5% for the controls (P < 0.005). Thirty-six (90%) patients in the group with nonobstructive a zoospermia (NOA) and 37 (92.5%) patients in the oligoteratoasthenospermia (OTA) group had embryos for replacement. The mean cleavage rates per cycle (96% with tasticular and 93% with ejaculated spermatozoa), the mean number of embryos per transfer (3.72 ± 1.6 in the NOA group and 4.24 ±1.5 in the OTA group), the embryo quality (cumulative embryo scoring = 34.03 ± 22.62 in the testicular sperm group and 36.08 ± 19.28 in the ejaculated sperm group), and the clinical pregnancy rates (22.5% in the NOA patients and 20% in the ejaculate group) were not significantly different between groups. Conclusions: High fertilization, cleavage, and pregnancy rates can be achieved with intracytoplasmic testicular sperm injection from patients with NOA, reaching levels comparable with those of ICSI using ejaculated spermatozoa.

Purpose:Our purpose was to assess whether one or more sperm parameters have predictive value for the outcome of intrauterine insemination treatment. Methods:Infertile couples whose normoovulatory and normomechanical female partners underwent superovulation and intrauterine insemination were investigated. The semen profile of the male partner was discounted. In 160 couples, 544 cycles were obtained, resulting in 59 ongoing pregnancies (10.84%/cycle, 36.87%/patient). Results:The only parameter found to be significantly correlated with a positive outcome was the degree of sperm motility following preparation for intrauterine insemination. Close to half (47.5%) of the couples with a very good or an excellent degree of sperm motility conceived, whereas only 8.3% of those patients who had poor or fair sperm motility conceived. None of the semen characteristics, such as volume, count, percentage motility, or percentage normal morphology, were found to correlate with cycle outcome. Although there was a progressive increase in the pregnancy rate with an increase in the total number of motile sperm inseminated, it did not reach significance. Seventy percent of the pregnancies were achieved within a maximum of three treatment cycles. The spermatogram is not accurate enough as a prognostic factor for treatment outcome. Conclusions:The degree of sperm motility, after appropriate preparation for intrauterine insemination, is the only parameter to be correlated with treatment outcome. For couples with a normal female partner, we suggest a maximum of three treatment cycles of induction of ovulation and intrauterine insemination, whenever good progressive motile sperm is obtained after suitable preparation. For cases with poor sperm progression, we suggest appropriate couple counseling and that an alternative assisted reproduction procedure be taken into consideration.

The two main conservative treatment alternatives for tubal pregnancy, methotrexate administration and laparoscopic salpingostomy are under constant review. Recently, expectant management of tubal pregnancy has become increasingly popular. In this review, we assess the outcome of conservative management modalities for extrauterine pregnancy and compare the results of treatment with methotrexate and operative laparoscopy. Outcomes of extrauterine pregnancy were obtained from a review compiled from the English literature identified by directed Medline search. Methotrexate and laparoscopic salpingostomies yield good final treatment rates of 85-95% respectively and relatively low rates for further surgical complication (5-10% respectively). Tubal patency, as well as future fertility performance, are quite similar after both techniques. Although they appear to suit the demands of the 21st century, each one has its own benefits and contraindications. With adequate patient selection, expectant management of the tubal pregnancy is a reasonable approach with good results. Although the morbidity rate after tubal pregnancy treatment is decreasing and the main concern is to reduce the decline in fertility potential, the real future challenge remains prevention of the disease, especially among high risk patients, such as those undergoing infertility treatment.

A new technique that combines saline contrast hysterosonography with three-dimensional surface rendering for the visualization of uterine intracavitary pathologies is described. A total of 32 patients suspected of having uterine cavity pathologies on the basis of previous ultrasonography, hysterosalpingography or hysteroscopy were involved in the study. They were examined by three-dimensional high-frequency endovaginal probes (Combison 530, Kretztechnik, Zipf, Austria), with normal saline used as an expander and contrast medium. Three perpendicular planes could be evaluated simultaneously, and surface renderings were readily available. Following the instillation of normal saline, the uterine cavity appears as an echo-free, well-defined structure, and the endometrium appears as an echogenic homogeneous lining around the cavity. Data acquisition time is short and images can be stored for later evaluation. Surface rendering of polypoid structures shows ecbogenie masses on a pedicle protruding into the uterine cavity. Submucous fibroids appear as mixed echogenic sites bulging into the cavity. Intrauterine synechiae appear as bands of varying thickness traversing the uterine cavity. Simultaneous display of the zone of interest in three perpendicular planes enhances imaging capabilities, while surface rendering provides a comprehensive overview of the surface area of the findings and their topographical orientation. Further research using this new technique is required to document its real contribution to ultrasonographic imaging. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology

Correct detection of premature contractions and incompetent uterine cervix is still a challenging obstetrical problem since these factors remain a major cause of perinatal loss. Ultrasonography offers additional important data for the prediction of these pathologies which have common sonographic patterns; shortening of the cervical length, funneling of the membranes and dilatation of the endocervical canal. The first section of this review highlights sonography of normal cervical anatomy, while the second section focuses on recent advances in sonographic detection of premature contractions and incompetent cervix. It is believed that due to its accuracy and reproducibility, this noninvasive technique should become more integrated into this aspect of antenatal care.

Objective: Our purpose was to assess and clarify the mechanism of whether an early progesterone rise in cycles with gonadotropin-releasing hormone agonist (GnRH-a) is associated with an impairment of IVF outcome Methods: Seven hundred eighty-six cycles were induced with GnRH-a and human menopausal gonodotropin (hMG) (“long protocol”). Plasma progesterone (PP) levels on the day of human chorionic gonadotropin (hCG) administration were divided into three groups: 2 ng/ml (Group C). We also analyzed the pregnancies achieved in our egg donation protocol in relation to the PP levels of each donor on the day of hCG administration. Results: Group A involved 525 cycles, Group B had 223, and Group C had 38. The overall pregnancy rate per egg transfer was 19.2%, with the highest for Group A (22.3%), declining for Groups B (14.3%) and C (7.9%) (A = B = C; P

Weekly serum Β-hCG measurements and transvaginal ultrasound scans coupled with color Doppler flow were performed on 8 patients with hydatidiform mole. Two patients later developed persistent trop