Outcome of gestational surrogacy according to IVF protocol.

PURPOSE: Surrogacy remains the only option for having a biologic child for a unique population of women with severe medical conditions. However, no study has looked at surrogacy outcome as a result of the type of ovarian stimulation of the intended mother [controlled ovarian stimulation (COH), modified natural cycle (MNC), and in vitro maturation (IVM)] for oocyte retrieval. METHODS: This is a retrospective study, including all intended mothers and gestational carriers in a tertiary, university affiliated, medical center, from 1998 to 2016. RESULTS: Fifty-two women underwent 252 oocyte retrieval cycles. The pregnancy outcome of 212 embryo transfer cycles (64 gestational carriers) was reviewed according to the origin of the embryo. The number of retrieved oocytes was significantly higher following COH (n = 132) compared with IVM (n = 58) and MNC cycles (n = 62) (p = 0.013 and p < 0.0001, respectively). Pregnancy rates for embryos transferred according to each protocol were similar. All pregnancies that ended in live births when oocytes from IVM cycles were used derived from transfers of retrieved mature and mixed mature and immature oocytes. Pregnancies that involved embryos derived solely from immature oocytes that further matured in vitro and were transferred to gestational carriers were unsuccessful. CONCLUSIONS: MNC protocol is a good option to achieve pregnancy for intended mothers using gestational surrogacy who have contraindications to COH. The yield of IVM cycles in which immature oocytes are retrieved is inconclusive.

Outcome of early versus late multifetal pregnancy reduction.

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.

FMR6 may play a role in the pathogenesis of fragile X-associated premature ovarian insufficiency.

The aim of this study was to evaluate whether long noncoding RNA accumulation play a role in the pathophysiology of fragile X-associated premature ovarian insufficiency (FXPOI). The study population consisted of 22 consecutive fragile X mental retardation 1 (FMR1) premutation carriers (CGGn 55-199 repeats) undergoing in vitro fertilization and pre-implantation genetic diagnosis (IVF-PGD) treatment. The control group consists of 11 patients, with <55 CGG repeats, undergoing IVF-ICSI for male factor infertility, matched by age, treated in the same period. After oocyte retrieval, granulosa cells from follicular fluid were washed and stored at -80 °C. RNA was transcribed to generate cDNA and the RNA levels were measured using RT-PCR. Transcripts levels in granulosa cells of long noncoding RNA's FMR4 and FMR6 were measured. In FMR1 premutation carriers there was a significant nonlinear association between the number of CGG repeats and the levels of FMR6 (p = 0.03), but not FMR4. The highest level of FMR6 was seen in women with mid-size CGG repeats (80-120). In addition, a significant negative linear correlation was observed between the number of oocytes retrieved and the RNA levels in granulosa cells of FMR6 (r = -0.53, p = 0.01) but not FMR4. Our study supports previous findings suggesting RNA toxic gain-of-function as one of the possible pathophysiologic mechanisms underlying FXPOI.

Pregnancy outcome of early multifetal pregnancy reduction: triplets to twins versus triplets to singletons.

Multifetal pregnancy reduction (MPR) of triplets to twins results in improved pregnancy outcomes compared with triplet gestations managed expectantly. Perinatal outcomes of early transvaginal MPR from triplets to twins were compared with reduction from triplets to singletons. Seventy-four trichorionic triplet pregnancies that underwent early transvaginal MPR at 6-8 weeks gestation were included. Cases were divided into two groups according to the initial procedure: reduction to twin (n = 55) or to singleton (n = 19) gestations. Infants from triplet pregnancies reduced to twins were delivered earlier (36.6 versus 37.9 weeks; P = 0.04) and had lower mean birth weights (2364 g versus 2748 g; P = 0.02) compared with those from triplets reduced to singleton gestations. The rates of pregnancy loss before 24 weeks (3.6% versus 5.3%), as well as of preterm delivery before 32 and 34 weeks of gestation (0% versus 5.3% and 7.3% versus 5.3%, respectively) were similar between the twin and singleton pregnancies. No significant difference was found in the prevalence of gestational diabetes (15.1% versus 5.6%) or gestational hypertension (24.5% versus 16.7%) between the groups. Selective reduction of triplet pregnancies to singleton rather than twin gestations is associated with improved outcomes.

Reactive oxygen species in follicular fluid may serve as biochemical markers to determine ovarian aging and follicular metabolic age.

INTRODUCTION: The aim of this study was to evaluate the role of oxidative stress in the process of ovarian aging. METHODS: Follicular fluid (FF) from two randomly selected sibling follicles was collected from women undergoing in-vitro fertilization and tested for hydrogen peroxide (H(2)O(2)) levels. RESULTS: Group A consists of seven women with whom each of the two sibling separate follicle yielded an oocyte that was later discordantly developed to a low- and top-quality embryo. Group B consists of 13 patients in whom one of the sibling follicle yielded an oocyte while the other did not (empty follicle). High-quality embryos were derived from follicles with lower H(2)O(2) levels compared to follicles from which poor-quality embryos developed (1.004 units ± 0.260 versus 1.145 units ± 0.236, p < 0.02). H(2)O(2) levels were significantly higher (0.951 units ± 0.233 versus 0.623 units ± 0.309, p < 0.001) in sibling follicles containing oocyte compared to empty follicles. CONCLUSION: During the process of ovarian ageing, there might be a gradual increase in H(2)O(2) level in the follicle. Finally, when the follicle ages and becomes empty of oocyte H(2)O(2) levels drops significantly. Therefore, H(2)O(2) levels in FF may serve as a possible marker to determine ovarian aging and follicular metabolic age.

Aneuploidy rates for chromosomes X/Y and 18 among preselected spermatozoa in men with severe teratospermia.

Eight infertile men with various degrees of oligoasthenoteratozoospermia and repeated implantation failure were selected for this study due to exceptionally high rates of sperm aneupoidy in their ejaculates. All subjects had normal physical examination, karyotype and serum FSH concentration. Prior to IVF treatment, spermatozoa was collected, processed, micromanipulated and tested for chromosomes X, Y and 18 using fluorescence in-situ hybridization. Aneupoidy rates for chromosomes X, Y and 18 were determined among sperm population selected for normal morphology using high-order magnification light microscopy. A second group of fast motile spermatozoa were collected using an intracytoplasmic sperm injection pipette from the medium-oil interface from microdroplets. The average aneuploidy rates for the three chromosomes were 7.6% (395/5182) in the sperm specimen before selection, 8.7% (116/1326) in the normal morphology selected group and 4.3% (59/1388; P<0.001) in the fast motile selected group. In conclusion, high-magnification light microscopy aimed at selection of spermatozoa with normal morphology did not affect the aneuploidy rate. On the other hand, fast motile spermatozoa harboured significantly less chromosomal abnormalities (P<0.001). Preselection of the most rapid sperm subpopulation for intracytoplasmic sperm injection may improve the qualities of the fertilizing spermatozoon.

Spontaneous conceptions following successful ART are not associated with premature referral.

STUDY QUESTION: What is the rate of spontaneous live births after successful IVF treatment in a cost-free environment, and were couples who achieved a spontaneous live birth referred prematurely? SUMMARY ANSWER: Despite unlimited IVF treatments offered free of charge, the spontaneous live birth rate following successful IVF remained unchanged compared with that cited in previous literature. Couples were not referred prematurely to IVF before fully utilizing other less invasive treatments. WHAT IS KNOWN ALREADY: A significant number of infertile couples, who achieve their first live birth through assisted reproductive technology (ART), subsequently achieve a second live birth spontaneously. As IVF has become more widely available, it is used in less severe cases of infertility, perhaps explaining a rise in the subsequent spontaneous live birth rate after successful treatments. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study was performed at a university-based tertiary medical center. The study population included women aged <35 years, with primary infertility, referred for their first IVF treatment to the Sheba Medical Center IVF unit between 2001 and 2002 and followed up for 7 years. The primary outcome was spontaneous live birth rate following successful ART. Relevant data were obtained from the patient files and supplemented by a standardized telephone questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 171 couples who met the study inclusion criteria, 6 refused to participate in the questionnaire and 31 couples were lost to follow-up. Of the 134 couples who participated, 109 achieved a first live birth with ART. After achieving their first live birth with ART, seven couples who began using contraception or separated or divorced were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Of 102 couples who continued unprotected intercourse after successful ART, 22 subsequently achieved their second live birth spontaneously (21.6%). The women who achieved a second birth spontaneously were not referred earlier to IVF, and actually performed a higher number of ovulation induction cycles before initiating IVF, compared with women who did not conceive spontaneously. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective cohort study, and findings should be reaffirmed with a larger prospective randomized study comparing retreatment to achieve a second pregnancy with attempting to conceive spontaneously. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggests that young patients (<35 years), who previously conceived with IVF, without utilizing ICSI and with no known tubal pathology, should consider attempting to conceive spontaneously. STUDY FUNDING AND COMPETING INTEREST(S): No funding was obtained for this study and the authors have no competing interests.

ICSI increases ongoing pregnancy rates in patients with poor response cycle: multivariate analysis of 2819 cycles.

The objective of this study was to evaluate the prognosis of patients with a first treatment cycle that was defined as a poor ovarian response cycle according to the new ESHRE consensus criteria. The first documented cycle of poor response for a patient and all the cycles that followed were retrospectively analysed. Factors that were associated with ongoing pregnancy rates were assessed using multivariate analysis. In total, this study evaluated 1014 patients that underwent 2819 consecutive IVF cycles. As expected, patients with poor response cycles were older and had less oocytes retrieved and less embryos transferred. Multivariate analysis for ongoing pregnancy rates adjusted for patient and the cycle characteristics revealed that the intracytoplasmic sperm injection (ICSI) procedure was associated with a significant increase of 40% in ongoing pregnancy rate (adjusted success ratio 1.40, 95% CI 1.00-1.96). Age over 41 years and additional cycles with poor response, were associated with significantly less ongoing pregnancy rate. However, the cumulative pregnancy rates were 29.5% and 36.4% following five and seven cycles, respectively. In conclusion, performing ICSI may improve the ongoing pregnancy rates in poor responders. Further studies are needed to establish the number of cycles recommended in these patients. Patients with poor ovarian response cycles are currently the most challenging group of fertility patients. We are yet far from understanding the factors which cause reduced ovarian response and further away from finding a solution to this painful problem. In this work, we present that with current available treatment modalities, the results can be improved. We show that performing intracytoplasmic sperm injection and implementation of additional number of treatment cycles may improve the ongoing pregnancy rates of patients with a first treatment cycle that is defined as a poor ovarian response cycle. In addition, we investigated the cumulative pregnancy rates in this group and the effect of performing a number of treatment cycles.

Anti-Müllerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes.

This study investigated anti-Müllerian hormone (AMH) expression and secretion from cumulus granulosa cells (GC) and steroidogenesis in follicular fluids (FF) with relation to oocyte maturational stages and fertilization capacity in large preovulatory follicles. This prospective study included 53 ovulatory women undergoing intracytoplasmic sperm injection. FF and cumulus GC from 140 large preovulatory follicles were individually obtained during oocyte retrieval. Main outcome measures were oocyte maturation, fertilization and embryo quality. FF were assayed for AMH, progesterone, 17ß-oestradiol and testosterone. Cumulus GC were assayed for AMH mRNA expression. AMH mRNA expression and secretion in cumulus GC in preovulatory follicles containing germinal-vesicle (GV) and metaphase-I (MI) oocytes were significantly higher than follicles containing MII oocytes (P<0.01 and P<0.0001, respectively). In addition, FF AMH concentrations from atretic oocytes were significantly higher than from MII oocytes. No correlation was found between AMH expression and secretion to fertilization or embryo quality. FF of MI and GV oocytes had higher concentrations of testosterone and lower progesterone/oestradiol ratios than MII oocytes, and FF of atretic oocytes contained higher testosterone concentrations than FF of MII oocytes. AMH is highly expressed in and secreted from cumulus GC of preovulatory follicles containing premature and atretic oocytes. Anti-Müllerian hormone (AMH) is produced in the female exclusively by granulosa cells. AMH has recently been shown to be one of the most important markers of ovarian reserve and it is highly associated with ovarian follicular development. This study investigates AMH expression and secretion from cumulus granulosa cells (GC) and steroidogenesis in the follicular fluids (FF) with relation to oocyte maturational stages, and fertilization capacity in large preovulatory follicles. We conducted a prospective study with 53 ovulatory women undergoing intracytoplasmic sperm injection. FF and cumulus GC from 140 large preovulatory follicles were individually obtained during oocyte retrieval. The main outcome measures were oocyte maturation, fertilization and embryo quality. FF were assayed for AMH, progesterone, 17ß-oestradiol and testosterone. Cumulus GC were assayed for AMH mRNA expression. AMH mRNA expression in cumulus GC and AMH concentrations in FF of preovulatory follicles containing premature oocytes (germinal vesicle (GV) and metaphase I (MI)) were significantly higher than preovulatory follicles containing mature oocytes (MII oocytes). In addition, FF AMH concentrations of atretic oocytes were significantly higher than FF AMH of MII oocytes. No correlation was found between AMH expression and secretion for fertilization or embryo quality. FF of preovulatory MI and GV oocytes had higher levels of testosterone and lower progesterone/oestradiol ratios than MII oocytes, and FF of atretic oocytes contained higher testosterone levels than FF of MII oocytes. This study shows that AMH is highly expressed in and secreted from cumulus GC of preovulatory follicles containing premature and atretic oocytes.

Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial.

AIM: To evaluate the effect of local injury to the endometrium during spontaneous menstrual cycles before in vitro fertilization (IVF) treatment on implantation and pregnancy rates in women with recurrent implantation failure (RIF). METHODS: In a prospective randomized controlled trial (RCT), a total of 36 patients, with RIF undergoing IVF, were randomized to two groups. In 18 patients, endometrial biopsies were performed using a pipelle curette on days 9-12 and 21-24 of the menstrual cycle preceding IVF treatment. In 18 control patients, a cervical pipelle was performed. RESULTS: The implantation rate (2.08% versus 11.11%; p = 0.1), clinical (0% versus 31.25%; p < 0.05) and live births rates (0% versus 25%; p = 0.1) were lower in the experimental group compared with controls. CONCLUSION: Our RCT did not find any benefit from local injury to the endometrium in women with a high number of RIFs. Further studies are warranted to better define the target population of patients who may benefit from this procedure.

Expression and regulation of sFRP family members in human granulosa cells.

Follicular development and ovulation are major processes in the reproductive system. Understanding their complexity is important to female fertility treatments and the control of reproductive processes. Wnt signaling pathway components were shown to be involved in reproduction in animal models. The secreted frizzled-related protein-4 (sFRP4), a potential modulator of Wnt4 signaling pathway, was shown to be induced by LH in rodents and expressed in the corpus lutea, but the pattern of its expression in human ovaries remains unknown. We evaluated the expression pattern of sFRP4 and other sFRP family members in human mural and cumulus granulosa cells (GCs), as well as their regulation by LH/hCG. GCs were obtained from follicles aspirated during in vitro maturation and IVF procedures. GCs were also plated and grown in culture. We showed that the human sFRP4 expression decreases as follicles grows to the preovulatory stage and its expression was higher in cumulus GCs than in mural GCs. Interestingly, LH/hCG stimulation of GCs in vivo and in culture resulted in decreased expression of sFRP4. Of the other sFRP family members, sFRP5 expression was found in mural and cumulus GC in vivo and was shown to be induced by LH/hCG in vitro and in vivo. In summary, sFRP4 is expressed in human GCs and its expression declines during late antral follicular growth. sFRP4 expression is also inhibited by LH/hCG, unlike its rodent homolog. In human GC, sFRP5 may substitute the role of sFRP4 in mouse GC.

Preimplantation genetic haplotyping a new application for diagnosis of translocation carrier's embryos- preliminary observations of two robertsonian translocation carrier families.

PURPOSE: Preimplantation genetic diagnosis using fluorescence in-situ hybridization (PGD-FISH) is currently the most common reproductive solution for translocation carriers. However, this technique usually does not differentiate between embryos carrying the balanced form of the translocation and those carrying the homologous normal chromosomes. We developed a new application of preimplantation genetic haplotyping (PGH) that can identify and distinguish between all forms of the translocation status in cleavage stage embryos prior to implantation. METHODS: Polymorphic markers were used to identify and differentiate between the alleles that carry the translocation and those that are the normal homologous chromosomes. RESULTS: Embryos from two families of robertsonian translocation carriers were successfully analyzed using polymorphic markers haplotyping. CONCLUSIONS: Our preliminary results indicate that the PGH is capable of distinguishing between normal, balanced and unbalanced translocation carrier embryos. This method will improve PGD and will enable translocation carriers to avoid transmission of the translocation and the associated medical complications to offspring.

Symposium: Update on prediction and management of OHSS. Prevention of OHSS: GnRH agonist versus HCG to trigger ovulation.

Ovarian hyperstimulation syndrome (OHSS) remains a major complication of IVF. Triggering ovulation with human chorionic gonadotrophin (RCG) (as a surrogate to LH) is a major factor in the initiation of OHSS. The pathological process usually intensifies if pregnancy is achieved, as the rising endogenous HCG overstimulates the corpora lutea. Decreasing HCG trigger dose does not prevent OHSS. Gonadotrophin-releasing hormone agonists (GnRHa) induce endogenous LH and FSH surges that reliably trigger ovulation, even if a GnRH antagonist is used during ovarian stimulation. Moreover, such a trigger quickly and irreversibly induces luteolysis, thereby preventing OHSS. Contrasting reports regarding clinical outcome probably reflect different approaches to luteal phase support. Zygotes or embryos frozen post GnRHa trigger give excellent clinical outcome post thaw. In summary, GnRHa trigger is the key for complete OHSS prevention.

Assisted reproduction in women over 40 years of age: how old is too old?

Women's fertility progressively declines with advanced age due to depletion of the ovarian follicular reserve and poorer oocyte quality. However, many women of advanced age are eager to conceive from their own ova. The aim of the present study was to evaluate the outcome of IVF cycles among older patients. All IVF retrievals performed in the unit in patients >or=42 years old between 1998 and 2006 were retrospectively analysed. Data were compared with patients <35 years old treated in the unit during the same time period. A total of 843 IVF retrievals in 459 patients >or=42 years old were assessed. Clinical pregnancy rates per cycle were 7.7%, 5.4% and 1.9% for 42, 43 and 44 years old, respectively. Only one IVF cycle in patients aged 44 years resulted in delivery. None of the 54 cycles performed in women of 45 years or older resulted in a pregnancy. A marked decline in clinical pregnancy and delivery rates, accompanied by an increase in spontaneous abortion rates, was found in patients >or=42 years old. In view of these results and as the option of egg donation is a promising alternative with delivery rates close to 50%, it appears that IVF treatment should be limited to patients not older than 43 years old with adequate ovarian response.

Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients.

BACKGROUND: Storing ovarian tissue for fertility preservation in cancer patients carries the risk of the presence of malignant cells that could lead to recurrence of cancer after reimplantation. Methods to exclude presence of cancer cells were used to improve the safety of cryopreservation-reimplantation procedures. METHODS: Fifty-eight patients with hematological malignancies were referred for the storage of ovarian tissue for fertility preservation. Investigation included preoperative imaging and histological evaluation of fresh ovarian tissue. After thawing markers to detect minimal residual disease (MRD) were used and compared with patient's disease used as positive control (five patients). RESULTS: Preoperative imaging detected disease in the ovaries (two patients). Conventional histology post-tissue harvesting did not disclose malignant cells (56 patients). MRD results post-thawing were negative in Hodgkin's disease (CD30 immunohistochemical staining), in T- and B-cell lymphoma (PCR for T-cell receptor and Ig clones, respectively) and in two chronic myelogenous leukemia patients (RT-PCR for BCR-ABL gene expression). However, highly sensitive real-time RT-PCR was positive in one CML patient and, this alarming result avoided tissue transplantation. CONCLUSIONS: Preoperative imaging prevented operations and storage of tissue with cancer. Evaluation of stored ovarian tissue for MRD using sensitive markers is essential to increase safety and to prevent reimplantation of tissue with malignant cells.

Ovarian tissue cryopreservation in hematologic malignancy: ten years' experience.

Cryopreservation of ovarian tissue is currently practiced in an attempt to preserve fertility before commencing potentially sterilizing chemotherapy. Clinical and laboratory guidelines are needed to standardize the procedure. Over the last 10 years ovarian tissue was stored in female patients with hematologic malignancies. Patients' records and consultation charts were evaluated, surgical and laboratory reports were revised and ovarian histology was investigated. Fifty-six patients with hematologic malignancies (age 24 +/- 5.5) had cryopreserved ovarian tissue. Thirty-three patients had Hodgkin's disease, 14 non-Hodgkin's lymphoma, 6 acute leukemia, and 3 chronic myelocytic leukemia. Harvesting of ovarian tissue was also performed following previous exposure to chemotherapy (33 patients), 13 of them shortly after the chemotherapy. Partial oophorectomy was the preferred surgical procedure. Fertility was restored with ovarian tissue transplantation in a sterilized patient and following fertility treatment in a patient with very low ovarian reserve. We recommend that indications and timing of ovarian tissue banking should be individualized. Patients previously exposed to chemotherapy can consider ovarian tissue freezing. The extent of tissue removed should take into account the large number of follicles lost and the risk of future sterilization. Tissue handling should enable further investigation of primordial follicles and identification of cancer cells.

[Oocytes in-vitro maturation--a new technique for reproductive endocrinologist practitioners].

In vitro maturation is a new and promising technique in the field of artificial reproductive technology. This method provides an alternative treatment to the known treatments and a solution for one of the most common and disturbing problems of infertility treatment, the hyperstimulation syndrome. The method is particularly useful in cases of patients with polycystic ovarian syndrome. The physiological process of oocyte maturation requires maturation of the nucleus and maturation of the oocyte cytoplasm. In the process of in vitro maturation of the oocyte, oocytes in their late stages of maturation are aspirated from the follicles and transferred to specific culture conditions to achieve complete maturation. The process of oocyte retrieval from small and undeveloped follicles needs proper equipment and experience. Therefore, this process requires deep understanding of the physiological process of oocyte and follicles growth and maturation, proper equipment and especially good experienced laboratory support. This review aims to describe the physiological basis for the process, the recommended protocols and to report the experience published so far on success rates and treatment safety, both maternal and fetal.

Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro.

Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01µg/mL, 0.1µg/mL, 1µg/mL, 10µg/mL, or 100µg/mL) for 48h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100µg/mL DBP resulted in significantly lower 17ß-estradiol and progesterone production (p<0.01). It also resulted in altered mRNA expression of steroidogenic, angiogenic, and epidermal growth factor-like growth factor genes: CYP11A1 (p<0.001), CYP19A1 (aromatase) (p<0.001), VEGF-A (p<0.02), BTC (p=0.009), and EREG (p=0.04). StAR expression was impaired after exposure to both 10 and 100µg/mL (p<0.03 and p<0.001, respectively). Our results indicate that in vitro exposure of granulosa cells to high doses of DBP alters cell functions.

Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria.

OBJECTIVE: To report the single-center results of orthotopic retransplantations of cryopreserved ovarian tissue in cancer survivors and evaluate the validity of commonly accepted procedure limitations. DESIGN: Prospective cohort study. SETTING: Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers. PATIENT(S): Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive. INTERVENTION(S): Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF). MAIN OUTCOME MEASURE(S): Endocrine profile, IVF, pregnancies, live births. RESULT(S): The patient ages at tissue harvesting ranged from 14 to 39 years. Fifteen women had hematologic malignancies, and two had leukemia (chronic myelogenous leukemia and acute myelogenous leukemia). Ten patients were exposed to nonsterilizing chemotherapy before OTCP. After transplantation, the endocrine recovery rate was 93%. Fourteen patients underwent IVF treatments with a fertilization rate of 58%. Sixteen pregnancies were achieved (10 after IVF, 6 spontaneous), resulting in 10 live births, two (twins) after harvesting from the mother at the age of 37. Two pregnancies are currently ongoing. After transplantation, 53% of patients conceived, and 32% delivered at least once. One patient conceived four times. Preharversting chemotherapy exposure was not associated with inferior outcomes. All patients, including two leukemia survivors, remained cancer free. CONCLUSION(S): Orthotopic transplantation of thawed ovarian tissue is a highly effective measure to restore fertility in sterilized cancer patients. Chemotherapy exposure before harvesting and age >35 is a realistic option in selected patients. Retransplantation in leukemic patients is possible after application of maximal safety measures. These results have led the national ethical and professional authorities to decide for the first time not to consider OTCP as an experimental modality for fertility preservation. CLINICAL TRIAL REGISTRATION NUMBER: NCT02659592.

Comparison of zygote intrafallopian tube transfer and transcervical uterine embryo transfer in patients with repeated implantation failure.

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.