Kfar Saba, Israel
Kfar Saba, Israel

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Donnez J.,Catholic University of Louvain | Silber S.,St Lukes Hospital | Andersen C.Y.,Copenhagen University | Demeestere I.,Free University of Colombia | And 4 more authors.
Annals of Medicine | Year: 2011

Introduction. Premature ovarian failure (POF) can occur naturally at an early age or be due to iatrogenic agents. Indeed, ovaries are very sensitive to cytotoxic treatment, especially to radiation and alkylating agents. Methods. Several options are currently available to preserve fertility in cancer patients and allow them to conceive when they have overcome their disease: embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. Cryopreservation of ovarian tissue is the only option available for pre-pubertal girls and women who cannot delay the start of chemotherapy. Findings. Since the first live birth after autotransplantation of cryopreserved ovarian tissue in humans was reported in 2004, orthotopic reimplantation has led to the birth of 13 healthy babies. Restoration of ovarian activity and prognostic factors are evaluated by comparison with 7 cases of fresh ovarian tissue transplantation. We report 13 live births after orthotopic transplantation of frozen-thawed ovarian tissue in cancer patients (n = 8) and in patients treated with high doses of chemotherapy for benign diseases (n = 2) (microscopic polyangiitis, sickle cell anemia). Interpretation. Based on our review, we believe that ovarian cortex cryopreservation, associated or not with cryopreservation of immature oocytes, should be offered before gonadotoxic chemotherapy in all cases where there is a high risk of POF and where emergency IVF is not possible. © 2011 Informa UK, Ltd.


Fatemi H.M.,Free University of Brussels | Popovic-Todorovic B.,Special Gynecology Hospital Ivanovic | Humaidan P.,University of Aarhus | Kol S.,IVF Unit | And 3 more authors.
Fertility and Sterility | Year: 2014

Objective To report two cases with GnRH agonist triggering and a freeze-all approach in a GnRH antagonist protocol resulting in the development of severe ovarian hyperstimulation syndrome (OHSS), requiring hospitalization and peritoneal drainage. Design Two case reports. Setting A tertiary referral center and an obstetrics and gynecology department of a hospital. Patient(s) Case 1 and case 2: severe OHSS with abdominal distension, ascites development, and hemoconcentration. Intervention(s) Case 1 and case 2: diagnosed by clinical, hematologic, and ultrasound findings. Hospitalization, IV infusion, and peritoneal drainage. Main Outcome Measure(s) Symptomatic treatment and prevention of further complication. Result(s) Complete recovery. Conclusion(s) Two cases of severe OHSS after GnRH agonist trigger in a GnRH antagonist protocol without the administration of any hCG for luteal-phase support. Clinicians have to be aware that even the sequential approach to ovarian stimulation with a freeze-all attitude does not completely eliminate OHSS in all patients. © 2014 American Society for Reproductive Medicine, Published by Elsevier Inc. All rights reserved.


Humaidan P.,Skive Regional Hospital | Kol S.,IVF Unit | Papanikolaou E.G.,Aristotle University of Thessaloniki
Human Reproduction Update | Year: 2011

Background: GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. Methods: This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. Results: In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. Conclusions: GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Imbar T.,Hebrew University of Jerusalem | Kol S.,IVF Unit | Lossos F.,Hebrew University of Jerusalem | Bdolah Y.,Hebrew University of Jerusalem | And 2 more authors.
Human Reproduction | Year: 2012

Background Triggering ovulation by GnRH agonist (GnRHa) in GnRH antagonist IVF protocols coupled with adequate luteal phase support has recently been suggested as a means to prevent ovarian hyperstimulation syndrome (OHSS). Our objective was to examine the outcome of fresh embryo transfer (f-ET) after triggering ovulation by GnRHa and providing intensive luteal phase supplementation, compared with that of the next first frozenthawed embryo transfer (ft-ET) after cycles with the same protocol and cryopreservation of all the embryos.Methods We performed a cohort study at a university-based IVF clinic. The study population was patients at high risk for OHSS. A daily dose of 50 mg i.m. progesterone in oil and 6 mg of oral 17-β-estradiol initiated on oocyte retrieval day in the f-ET group (n 70). In the ft-ET group (n 40) the embryos were cryopreserved and transferred in the next cycle. Results The live birth rate per f-ET was 27.1 versus 20 in the ft-ET groups [P 0.4; rate ratio 1.36 (0.652.81)]. The implantation, pregnancy and spontaneous abortion rates were comparable in both groups. None of the patients developed OHSS. Conclusions In this observational cohort study, we showed that triggering ovulation with GnRHa and intensive luteal phase support is a promising new modality to prevent OHSS without the cost of cycle cancellation, ET deferral and reduced clinical pregnancy rates. Confirmation of these findings by RCTs is now required. © 2012 The Author.


Ferraretti A.P.,IVF Unit | Gianaroli L.,IVF Unit | Magli M.C.,IVF Unit | Devroey P.,IVF Unit
Fertility and Sterility | Year: 2015

Objective To validate the use of clomiphene citrate in IVF when mild stimulation approaches are chosen to reduce patient discomfort, risk, and cost. Design Prospective cohort study. Setting Private IVF clinic. Patient(s) A total of 163 patients undergoing IVF and with a good prognosis (defined as ≤38 years old with normal ovarian reserve and normovulatory cycles, body mass index <29 kg/m, no previous assisted reproductive technology cycles, no severe endometriosis, no history of recurrent miscarriage, no endocrine/autoimmune diseases, and no surgical semen extraction). Intervention(s) Mild stimulation using a fixed protocol of clomiphene citrate (100 mg/d from cycle days 3 to 7) in combination with low doses of gonadotropins (150 IU of recombinant FSH on cycle days 5, 7, and 9) and GnRH antagonist. Main Outcome Measure(s) The cumulative delivery rate per patient after three fresh and/or frozen embryo transfers and time to pregnancy. Result(s) No dropouts were observed. The cumulative delivery rate was 70%, and the mean time to pregnancy was 2.4 months. Conclusion(s) Mild stimulation using clomiphene citrate in combination with low doses of gonadotropins can be considered a realistic option for good-prognosis patients undergoing IVF. © 2015 American Society for Reproductive Medicine.


Kol S.,IVF Unit | Humaidan P.,University of Southern Denmark
Reproductive BioMedicine Online | Year: 2013

The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. Recent developments in the area strengthen this premise. GnRHa trigger offers important advantages, including virtually complete prevention of ovarian hyperstimulation syndrome (OHSS), the introduction of a surge of FSH in addition to the LH surge and finally the possibility to individualize luteal-phase supplementation based on ovarian response to stimulation. We maintain that the automatic HCG triggering concept should be challenged and that the GnRHa trigger is the way to move forward with thoughtful consideration of the needs, safety and comfort of our patients. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.


Granot I.,IVF Unit | Gnainsky Y.,Weizmann Institute of Science | Dekel N.,Weizmann Institute of Science
Reproduction | Year: 2012

Implantation failure, which is presently the major barrier in human fertility, is attributed, in many cases, to the failure of the uterus to acquire receptivity. The transition into a receptive uterus includes cellular changes in the endometrium and the modulated expression of different cytokines, growth factors, transcription factors, and prostaglandins. These molecules partake in the generation of an inflammatory response followed by the recruitment of immune cells. These cells have shown to be involved in the maternal immune tolerance toward the implanted embryo as well as in the maternal-fetus interaction during pregnancy. Most of the accumulated evidence indicates that embryo implantation is associated with an active Th1 inflammatory response while a Th2-humoral inflammation is required for pregnancy maintenance. Yet, recent findings suggest that a Th1 inflammatory response is also necessary for the acquisition of uterine receptivity. This notion was originally suggested by reports from our and other clinical centers worldwide that IVF patients with repeated implantation failure subjected to endometrial biopsy exhibit a substantial improvement in their chances to conceive. These findings, followed by the demonstration of an elevated pro-inflammatory cytokine/chemokine expression, as well as an increased abundance of immune cells, in the endometrium of these patients, raised the idea that acquisition of uterine receptivity is closely associated with an inflammatory response. This review summarizes the molecular and biochemical evidence that confirm this notion and proposes a mechanism by which injury-induced inflammation improves uterine receptivity and the subsequent pregnancy outcome. © 2012 Society for Reproduction and Fertility.


Kol S.,IVF Unit | Humaidan P.,Odense University Hospital | Itskovitz-Eldor J.,IVF Unit
Human Reproduction | Year: 2011

Background 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. Results 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 E2 and progesterone levels were 6607 (±3789) and 182 (±50) nmol/l, respectively. Of the pregnancies, seven are ongoing, while four ended as miscarriages. Conclusions 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. © 2011 The Author.


The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF) embryos. Preimplantation genetic diagnosis (PGD) or screening (PGS) involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND) require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future. © 2014 Tanya Milachich.


Maman E.,IVF Unit | Meirow D.,IVF Unit | Brengauz M.,IVF Unit | Raanani H.,IVF Unit | And 2 more authors.
Fertility and Sterility | Year: 2011

Objective: To compare the results of in vitro maturation (IVM) of oocytes for fertility preservation performed during the luteal phase of the cycle with those of IVM performed during the follicular phase. Design: Retrospective chart review (August 2007 to June 2009). Setting: Academic tertiary referral fertility center. Patient(s): Cancer patients who underwent treatment for fertility preservation. Intervention(s): IVM treatment during either luteal or follicular phase. Main Outcome Measure(s): Number of oocytes, maturation and fertilization rates, and number of oocytes and embryos that were frozen. Result(s): Eighteen cancer patients underwent IVM fertility preservation, five in their luteal phase and 13 in their follicular phase. The baseline characteristics of both groups were similar. There were no significant differences in the number of retrieved oocytes, maturation rates, fertilization rates, or the total number of oocytes and embryos that were cryopreserved. Conclusion(s): These results suggest that IVM during the luteal phase can be offered to patients as an optional treatment for urgent fertility preservation when there is insufficient time for conventional follicular phase oocyte retrieval before chemotherapy must be initiated. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

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