Michal Lavee

Empty follicle syndrome: successful treatment in a recurrent case and review of the literature

Empty follicle syndrome is a condition in which no oocytes are retrieved after an apparently adequate ovarian response to stimulation and meticulous follicular aspiration. It is a rare condition of obscure etiology. A patient with primary infertility who underwent seven assisted reproductive technique cycles is described. In spite of a satisfactory ovarian response, aspiration yielded no oocytes in four cycles and 1-4 low quality oocytes in three cycles. In the index treatment cycle, ovulation was triggered using GnRH agonist 40 h prior to ovum pickup and hCG was added 6 h after the first trigger. Eighteen oocytes were recovered, of which 16 were mature and were inseminated by ICSI. Two embryos were transferred 48 h after aspiration and nine embryos were cryopreserved. The patient conceived and delivered a healthy boy at 38 weeks of gestation. The literature is reviewed and possible etiologies and treatment options of this enigmatic syndrome are suggested.

Rescue intracytoplasmic sperm injection: a systematic review

OBJECTIVE To assess the feasibility, efficacy, and safety of rescue intracytoplasmic sperm injection (ICSI) in cases of fertilization failure, using a scientific literature search. DESIGN Systematic review. SETTING Centers for reproductive care. PATIENT(S) Infertility patients with total or partial fertilization failure during an IVF cycle. INTERVENTION(S) An electronic literature search was performed in PubMed from 1992 through May 2013. The search was then expanded by using listed references from selected articles. MAIN OUTCOME MEASURE(S) Pregnancy rate. The secondary outcome measures were fertilization rate, normal fertilization rate, cleavage rate, birth rate, and malformation rate. RESULT(S) Thirty-eight studies including 1,863 patients were included. The pooled pregnancy rate was 14.4%; 194 babies were delivered. CONCLUSION(S) Rescue ICSI can result in the delivery of a healthy newborn, although the pregnancy rates are low. The clinical evidence did not indicate an elevated rate of malformations, although the data are limited and incomplete.

Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction.

Objective: To compare continuous with intermittent epidural infusion on the duration of labor and patients’ satisfaction in nulliparous women. Methods: Nulliparous women who requested epidural analgesia during labor were randomly allocated to receive either a continuous infusion of 0.125% bupivacaine with 2 &mgr;g/mL fentanyl at a rate of 8 mL/h (group A) or intermittent bolus of 10 mL of 0.25% bupivacaine on demand (group B). Controls were nulliparous women who did not receive epidural analgesia (group C). Included were singleton term pregnancies with cervical dilatation between 2 cm and 5 cm. A comparison was made between the groups regarding the duration of the active phase and the second stage of labor and patients’ satisfaction. Secondary outcomes investigated were the mode of delivery, analgesia-related complications, and intrapartum and postpartum complications. Cord pH and Apgar score measured neonatal outcome. Results: Sixty-three parturients were randomly assigned to receive continuous infusion, and 64 received intermittent bolus infusion. Sixty-three patients served as controls. Mean duration of the active phase and the second stage of labor were not statistically different between groups A and B. Each technique produced comparable analgesia, achieving equivalent maternal satisfaction, with no apparent complications. The active phase of labor was prolonged by an average of 60 minutes and the 2nd stage by an average of 36 minutes regardless of the type of epidural compared with controls. The mode of delivery and maternal and neonatal outcome were not significantly different among the 3 groups. Conclusion: This study provides evidence that both continuous and intermittent epidural infusion produce comparable analgesia achieving equivalent maternal satisfaction with no difference regarding the duration of labor between them. Although patients receiving epidural analgesia experienced longer labors compared with controls, both mothers and neonates were unharmed. Level of Evidence: I

Toxicological features of deliberate self-poisonings.

Background: Deliberate self-poisoning (DSP) is a major health problem with increasing incidence mainly among young people. Objective: To examine the clinical and toxicological characteristics of DSP, it is compared to unintentional (non-DSP) exposures and those characteristics which might be associated with increased toxicological risk are identified. Methods: Two-year retrospective poison centre chart review. Statistics: χ2 analysis. Results: 3802 DSP cases were reported. Most calls (95%) were made by physicians compared to 51%) in non-DSP exposures, P <0.0001. There were almost twice as many females as males, contrary to unintentional exposures (P <0.001). Peak frequency involvement was at the age of 15-20 years for females and older for males. Only 19.8%) of DSP calls were made within the first hour of exposure compared to 46%) of the non-DSP calls (P <0.001). Younger patients tended to present earlier. The vast majority of exposures occurred by ingestion and at home. Pharmaceuticals and chemicals were involved in 86% and 12% of DSP cases, respectively (compared to 29% and 44% in non-DSP exposures, respectively, P <0.001). Psychiatric drugs were more commonly used in older age groups and analgesics among the younger. Insecticides, sodium hypochlorite and rodenticides were the most frequently used chemicals. Neurological involvement was observed in 48.2% of DSP patients compared to 16.9% in non-DSP exposures. DSP was associated with greater severity than non-DSP exposures (21% and 10% had moderate to severe toxicity, respectively, P <0.001). Severity was greater among males, aged older than 45 years, with time from exposure to consultation 8 hours or longer and with exposure to chemicals, psychiatric drugs or combinations. Conclusions: Most DSP patients were females, aged 15-20 years, used pharmaceuticals and had neurological involvement. Males, aged over 45 years, with longer time to toxicology consult and the use of chemicals were associated with increased severity. These parameters should alert the treating physician to the possibility of a poor course and hence to a more aggressive therapeutic approach.

Matrix metalloproteinase-2 is elevated in midtrimester amniotic fluid prior to the development of preeclampsia

ObjectiveTo evaluate levels of matrix metalloproteinases (MMP) and their inhibitors (TIMP) in second trimester amniotic fluid of women with hypertensive disorders compared to normotensive women.Study DesignAmniotic fluid was obtained from 133 women undergoing genetic second trimester amniocentesis. Zymography was performed for MMP characterization and an MMP-2 ELISA kit was used to determine MMP-2 levels. TIMP-2 expression was evaluated using western blot.ResultsMean amniotic fluid MMP-2 and TIMP-2 levels were significantly higher in women who developed a hypertensive disorder compared to normotensive women (P < 0.0004 and P < 0.01, respectively). When subdivided into subgroups, amniotic fluid from women who eventually developed preeclampsia or superimposed preeclampsia showed significantly higher MMP-2 levels than normotensive women (P < 0.05). However, no statistical difference in MMP-2 levels was found between patients with gestational hypertension and normotensive patients.ConclusionHigher amniotic fluid MMP-2 and TIMP-2 levels are found in women who eventually develop preeclampsia.

Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study

BackgroundIn-vitro fertilization is a known risk factor for ectopic pregnancies. We sought to establish the risk factors for ectopic pregnancy in GnRH antagonist cycles examining patient and stimulation parameters with an emphasis on ovulation trigger.MethodsWe conducted a retrospective, cohort study of 343 patients undergoing 380 assisted reproductive technology (ART) cycles with the GnRH antagonist protocol and achieving a clinical pregnancy from November 2010 through December 2015.ResultsSignificant risk factors for ectopic pregnancy in the univariate analysis included prior Cesarean section (CS), endometriosis, mechanical factor infertility, longer stimulation, elevated estradiol and progesterone levels, GnRH agonist trigger, higher number of oocytes aspirated, and insemination technique. Independent risk factors for ectopic pregnancy in the multivariate analysis included GnRH agonist trigger, higher number of oocytes aspirated, insemination technique, and prior Cesarean section.ConclusionExcessive ovarian response, IVF (as opposed to ICSI), prior Cesarean section and GnRH agonist trigger were found to be independent risk factors for ectopic pregnancy. Caution should be exercised before incorporating the GnRH agonist trigger for indications other than preventing OHSS. When excessive ovarian response leads to utilization of GnRH agonist trigger, strategies for preventing ectopic pregnancy, such as a freeze all policy or blastocyst transfer, should be considered. Further studies should elucidate whether adjusting the luteal support can reduce the ectopic pregnancy risk.

Lag time from ovulation trigger to oocyte aspiration and oocyte maturity in assisted reproductive technology cycles: a retrospective study

OBJECTIVE To study the correlation between the lag time from ovulation trigger to oocyte aspiration and the proportion of metaphase II (MII) mature oocytes aspirated. DESIGN Retrospective study. SETTING Fertility and IVF center in an academic regional hospital. PATIENT(S) A total of 511 women undergoing IVF-intracytoplasmic sperm injection at our center, with at least one oocyte available for maturity determination. INTERVENTION(S) Data were retrieved from patient electronic databases and files. Demographic data, hormone treatments and ovarian response, and the time of ovulation trigger and oocyte aspiration were recorded. MAIN OUTCOME MEASURE(S) The primary outcome was the proportion of MII mature oocytes relative to the total number of oocytes aspirated and allocated to intracytoplasmic sperm injection. Pregnancy rates and clinical pregnancy rates were secondary outcomes. RESULT(S) There were fewer MII mature oocytes when the lag time between oocyte trigger and aspiration was between 33.45 hours and 34.45 hours. The proportion of MII oocytes seems to increase up to a 35-hour lag time and then stabilizes up to 38 hours. Pregnancy and clinical pregnancy rates did not differ among the different time groups studied. CONCLUSION(S) Oocyte aspiration should be scheduled at least 35 hours after ovulation trigger. Oocytes can be aspirated in a 3-hour window of time between 35 and 38 hours without compromising results. Further research should elucidate whether even longer lag times will improve the proportion of MII mature oocytes.

Outcome of twins delivery; predictors for successful vaginal delivery: a single center experience.

The aim of this study was to compare maternal and neonatal outcome of twin births according to mode of delivery and to isolate the factors predicting a successful vaginal delivery and those predicting a failed trial of labor (TOL) leading to an emergent cesarean section. We reviewed all twin deliveries during the years 1995 to 2004. Parameters studied include maternal age, parity, gestational age, maternal antepartum complications and postpartum complications, fetal presentations, birthweight, mode of delivery of each twin, Apgar scores and cord pH. During the study period there were 40,710 deliveries of which 804 (1.9%) were twin deliveries. Of the 804 twins, 398 (49.5%) had planned cesarean sections (PCS) and 406 (50.5%) entered a TOL. Maternal age and parity were similar among the groups. Neonatal outcomes and postpartum complications did not differ between the groups. Of 406 women who had a TOL, 84.9% eventually delivered both twins vaginally. A significantly higher percentage of antepartum complications were noted among those who failed the TOL compared to those with successful TOL (8.2% vs. 1.7%, p = .01). The number of neonates with pH of less than 7.0 did not differ between the groups although more neonates (2.5% vs. 0.4%, p = .05) among the failed TOL had an Apgar score of less than 7.0 at 5 minutes compared to successful TOL. Vaginal delivery of both twins after TOL occurred in 91% of vertex/vertex compared with 71.8% of vertex/nonvertex presenting twins (p < .01). Neonatal outcomes did not differ between both groups. Our results indicate that both vaginal and PCS are comparable options for vertex presenting first twin regardless of second twin presentation.

A randomized trial comparing time intervals from HCG trigger to intrauterine insemination for cycles utilizing GnRH antagonists

Abstract Intrauterine insemination (IUI) during ovarian stimulation cycles is typically performed 36 hours after human chorionic gonadotropin (hCG) injection. We hypothesized that adjusting the time interval to IUI to better coincide with ovulation may increase pregnancy rates. Patients undergoing induction of ovulation utilizing gonadotropins and gonadotropin releasing hormone (GnRH) antagonists and IUI were divided to three groups based on the time from hCG injection to IUI: 36, 42, and 48 hours. Primary outcome was defined as the clinical pregnancy rate. Secondary outcomes comprised additional parameters including multifetal pregnancy rate. A total of 92 patients completed the study. Baseline parameters were similar between the groups. The clinical pregnancy rate in the three groups was 20%, 38%, and 24%, respectively. While the 42 hour time interval had a higher numerical pregnancy rate, the pregnancy rates did not differ statistically among the study groups. The multifetal pregnancy rate did not differ among the three groups as well. A larger study is necessary to ascertain if a 42 hour time interval can indeed improve pregnancy rates.

Haptoglobin phenotypes and in vitro fertilization treatment outcomes

The haptoglobin (Hp) protein has been implicated in various aspects of reproduction. One possible mechanism is through its effect on angiogenesis. Angiogenesis plays a major role in follicle production. The Hp insertion polymorphism results in the production of Hp proteins denoted Hp 1-1, 2-1, and 2-2, with markedly different angiogenic activities. We sought to determine if the number of oocytes aspirated during in vitro fertilization is related to the Hp type and to compare clinical data and treatment outcomes. We conducted a prospective non-interventional study in an academic in vitro fertilization center serving northern Israel. All patients undergoing in vitro fertilization who agreed to have their haptoglobin phenotype and clinical data evaluated anonymously were included. The main outcome measure was the number of oocytes harvested from each aspiration. The groups did not differ regarding ethnicity or BMI, though women with the Hp1-1 phenotype had a longer duration of infertility (p = 0.037) and a higher gonadotropin requirement (p = 0.024) to achieve the same treatment outcome. Women with mechanical factor infertility were more likely (p = 0.042) to have the Hp 1-1/2-1 phenotypes than the Hp2-2 phenotype. There were no differences in the number of oocytes aspirated or the pregnancy rate. In summary, we could not establish a correlation between Hp phenotype and oocyte number or IVF outcomes though the Hp2-2 phenotype may be protective against mechanical factor infertility. Further studies with a larger sample size, particularly concerning the Hp1-1 phenotype, are required in order to extend these results.