Prophylactic SSRI treatment for women suffering from mood and anxiety symptoms undergoing in vitro fertilization-a prospective placebo-controlled study.

To explore the mood protective effect of prophylactic SSRI treatment on women undergoing IVF suffering from moderate affective and anxiety symptoms. In a randomized double blind, placebo-controlled, parallel design study, 41 women diagnosed with an Adjustment Disorder, who were undergoing IVF treatments, were randomized into two groups; a study group (n = 22) administered escitalopram 10 mg/day, and a control group (n = 19) administered placebo for a total of 8 weeks before and during the IVF treatment cycle. Patients were assessed at the onset of drug treatment and at embryo transfer. The main outcome measure was the difference in mean score severity rating of depression and anxiety symptoms on the CES-D and Zung questionnaires between groups at the time of embryo transfer. Secondary outcome measures included the MHI rating subscales addressing aspects of psychological distress and coping. At the day of embryo transfer (6 weeks of drug treatment), the CES-D average score for the treatment group was 6.40 (6.71) and 27.47 (4.29) on the Zung Self-Rating Anxiety Scale, while the placebo group scored an average of 15.83 (8.69) and 33.17 (6.95) receptively. These findings were significant (p = .004, p = .015 receptively) and were endorsed by the scoring on the MHI questionnaire subscales. Short-term treatment with SSRI may serve as a prophylactic treatment against the perpetuation and possible worsening of depressive and anxiety symptoms in women undergoing IVF treatments. Further studies concerning pharmacological interventions in larger samples and studies addressing screening for psychological stress indicators in this population are warranted.

Prolonged activation of the coagulation system during in vitro fertilization cycles.

OBJECTIVE: To investigate coagulation system changes during an in-vitro fertilization (IVF) cycle using Thromboelastogram (TEG) that enables analysis of the elastic properties of whole blood samples and provides a global assessment of the hemostatic function. STUDY DESIGN: A prospective study. TEG indices were evaluated in 23 women who underwent controlled ovarian stimulation for IVF at four points in time: 1. At the beginning of the cycle (corresponding to the lowest levels of E2), 2. On the day of hCG administration (maximal stimulation with highest E2 levels), 3. On the day of ovum pickup and 4. At the first pregnancy test (approximately 14days after ovum pickup). The main outcome measures were TEG indices including R-time (time until initial fibrin formation), K-time (time until a 20mm amplitude is achieved), α angle (the rate of clot formation), Maximum Amplitude (MA, strength of the fibrin clot), Coagulation Index (CI, calculated overall indicator of coagulation) and LY30 (the decrease in graph amplitude). RESULTS: R, K, α angle, MA and CI before hCG administration and at the time of the first pregnancy test were significantly higher compared to the baseline measurement before gonadotropins administration. No correlation was found between E2 and TEG indices. CONCLUSION: Ovarian stimulation is associated with prolonged increased coagulability that extends after the time of maximal ovarian stimulation. The lack of association between E2 levels and TEG indices suggest that additional factors may play a role in the pathogenesis of increased coagulability in women with ovarian stimulation.

Improving preimplantation genetic diagnosis (PGD) reliability by selection of sperm donor with the most informative haplotype.

BACKGROUND: The study is aimed to describe a novel strategy that increases the accuracy and reliability of PGD in patients using sperm donation by pre-selecting the donor whose haplotype does not overlap the carrier's one. METHODS: A panel of 4-9 informative polymorphic markers, flanking the mutation in carriers of autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before PGD. Whenever the lengths of donors' repeats overlapped those of the women, additional donors' DNA samples were analyzed. The donor that demonstrated the minimal overlapping with the patient was selected for IVF. RESULTS: In 8 out of 17 carriers the markers of the initially chosen donors overlapped the patients' alleles and 2-8 additional sperm donors for each patient were haplotyped. The selection of additional sperm donors increased the number of informative markers and reduced misdiagnosis risk from 6.00% ± 7.48 to 0.48% ±0.68. The PGD results were confirmed and no misdiagnosis was detected. CONCLUSIONS: Our study demonstrates that pre-selecting a sperm donor whose haplotype has minimal overlapping with the female's haplotype, is critical for reducing the misdiagnosis risk and ensuring a reliable PGD. This strategy may contribute to prevent the transmission of affected IVF-PGD embryos using a simple and economical procedure. TRIAL REGISTRATION: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. DNA testing of donors was approved by the institutional Helsinki committee (registration number 319-08TLV, 2008). The present study was approved by the institutional Helsinki committee (registration number 0385-13TLV, 2013).

A New Perspective on the Risk of Hypercoagulopathy in Ovarian Hyperstimulation Syndrome Using Thromboelastography.

Thromboelastography (TEG) provides real-time assessment of hemostasis by measuring the viscoelastic properties, coagulation factor, and platelet activity in whole blood samples. In this prospective case-control study, we wanted to investigate whether blood clot formation assessment, using TEG, can identify a hypercoagulable state in women with severe ovarian hyperstimulation syndrome (OHSS). Thirty-six women who were hospitalized with severe OHSS were allocated to the OHSS group and 32 women undergoing controlled ovarian hyperstimulation but who did not develop OHSS were allocated to the control group. The TEG indices were compared between women with severe OHSS and controls. All the coagulation indices assessed by TEG were significantly different in the OHSS group compared to the controls, depicting a hypercoagulable state. Median coagulation index was 3.6 (interquartile range: 2.80-4.15) and 1.45 (interquartile range: 0.20-2.30) in study group and controls, respectively ( P < .001). Our results show that TEG can be used to depict a hypercoagulable state in women with severe OHSS.

The effect of a germline mutation in the APC gene on ß-catenin in human embryonic stem cells.

BACKGROUND: Most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene, which is a negative regulator of the Wnt-ß-catenin pathway. Patients with familial adenomatous polyposis (FAP) inherit a germline mutation in one APC allele, and loss of the second allele leads to the development of polyps that will turn malignant if not removed. It is not fully understood which molecular mechanisms are activated by APC loss and when the loss of the second APC allele occurs. METHODS: Two FAP human embryonic stem cell (hESCs) lines were derived from APC mutated embryos following pre-implantation genetic diagnosis (PGD) for FAP. These FAP-hESCs were cultured in vitro and following extended culture: 1) ß-catenin expression was analyzed by Western blot analysis; 2) Wnt-ß-catenin/TCF-mediated transcription luciferase assay was performed; 3) cellular localization of ß-catenin was evaluated by immunoflorecence confocal microscopy; and 4) DNA sequencing of the APC gene was performed. RESULTS: We have established a novel human in-vitro model for studying malignant transformation, using hESCs that carry a germline mutation in the APC gene following PGD for FAP. Extended culturing of FAP1 hESCs led to activation of the Wnt signaling pathway, as demonstrated by enhanced ß-catenin/TCF-mediated activity. Additionally, ß-catenin showed a distinct perinuclear distribution in most (91 %) of the FAP1 hESCs high passage colonies. DNA sequencing of the whole gene detected several polymorphisms in FAP1 hESCs, however, no somatic mutations were discovered in the APC gene. On the other hand, no changes in ß-catenin were detected in the FAP2 hESCs, demonstrating the natural diversity of the human FAP population. CONCLUSIONS: Our results describe the establishment of novel hESC lines from FAP patients with a predisposition for cancer mutation. These cells can be maintained in culture for long periods of time and may serve as a platform for studying the initial molecular and cellular changes that occur during early stages of malignant transformation.

Donation of surplus frozen pre-embryos to research in Israel: underlying motivations.

BACKGROUND: The high number of IVF procedures performed in Israel has had an unforeseen consequence: accumulation of large amounts of surplus frozen embryos. After five years that the frozen embryos are kept for free, patients need to make an embryo disposition decision. One option is donation for research. The donation rate in Israel is very low. Our aim was to understand the attitudes, values and perceptions of female IVF patients that decided to donate their surplus frozen embryos to research. METHODS: The study setting was a tertiary IVF unit which during the 2000-2009 period treated 241 patients who had their frozen pre-embryos stored for more than five years. The study population consists of the 12 patients (from among the 241) who had decided to donate their excess frozen pre-embryos to research. In-depth interviews were carried out with 8 of those 12 patients. RESULTS: IVF patients who donated their surplus frozen pre-embryos to research viewed the frozen embryo as a valuable resource that does not have human identity yet. The majority expressed a gradualist approach to the human status of the embryo as requiring successful implantation and development in the uterus. All the respondents chose donation to research not because it was their first choice but because they did not want or were unable to use the pre-embryos in the future, in addition to not willing to thaw them. For many of the respondents, donation to research was accompanied by a sense of uncertainty. All would have preferred to donate their pre-embryos to infertile women or couples, an option which is currently prohibited in Israel. CONCLUSIONS: The moral reasoning behind decisions that patients make regarding excess pre-embryos is important for health care practitioners to consider when offering decision-making alternatives and counseling. For our respondents, the scarcity of donating excess frozen pre-embryos to research may reflect patients' preference for embryo donation to infertile couples. Recommended ways to increase donation to research may include public education and awareness, as well as targeted communication with IVF patients by multi-professional IVF unit teams comprised of a medical doctor and a professional trained in bioethics.

Blastomere biopsy for PGD delays embryo compaction and blastulation: a time-lapse microscopic analysis.

PURPOSE: The purpose of the study was to explore the effect of blastomere biopsy for preimplantation genetic diagnosis (PGD) on the embryos' dynamics, further cleavage, development, and implantation. METHODS: The study group included 366 embryos from all PGD treatments (September 2012 to June 2014) cultured in the EmbryoScope™ time-lapse monitoring system. The control group included all intracytoplasmic sperm injection (ICSI) embryos cultured in EmbryoScope™ until day 5 during the same time period (385 embryos). Time points of key embryonic events were analyzed with an EmbryoViewer™. RESULTS: Most (88 %) of the embryos were biopsied at ≥8 cells. These results summarize the further dynamic development of the largest cohort of biopsied embryos and demonstrate that blastomere biopsy of cleavage-stage embryos significantly delayed compaction and blastulation compared to the control non-biopsied embryos. This delay in preimplanation developmental events also affected postimplantation development as observed when the dynamics of non-implanted embryos (known implantation data (KID) negative) were compared to those of implanted embryos (KID positive). CONCLUSION: Analysis of morphokinetic parameters enabled us to explore how blastomere biopsy interferes with the dynamic sequence of developmental events. Our results show that biopsy delays the compaction and the blastulation of the embryos, leading to a decrease in implantation.

Molecular mechanisms regulating impaired neurogenesis of fragile X syndrome human embryonic stem cells.

Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the "GSK3ß theory of FXS" for the first time in a human-based model. We found no evidence for a pathological increase in GSK3ß protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system.

Israeli Druze women's sex preferences when choosing obstetricians and gynecologists.

BACKGROUND: Consideration and better understanding of patients' needs on the part of the healthcare system might help increase the number of people seeking necessary medical care. Many studies have been conducted on patients' preferences in choosing their health care provider, but the majority of them were conducted in modern western societies, establishing a need to explore other populations. The present study was performed in the Israeli Druze community which is composed of a uniquely traditional and religious population. We assessed the sex preference of Israeli Druze women regarding obstetricians/gynecologists, and identify other features that affect their choice. METHOD: We conducted a cross-sectional study that included 196 Israeli Druze women who anonymously completed a 36-item questionnaire between January-July, 2011. RESULTS: Most (63.8%) of the responders preferred female obstetricians/gynecologists, while 74.5% had no sex preference for their family physicians. 68.6% of the religious women preferred female obstetricians/gynecologists as compared to 51.76% of those women who self-identified as secular. Most of the women (65%) preferred female obstetricians/gynecologists for intimate procedures, such as pelvic examination and pregnancy follow-up. The main reasons given were: feeling more comfortable with a female practitioner (69.7%), the belief that females are more gentle (56.6%), and being more embarrassed with male obstetricians/gynecologists (45.4%). Three factors were associated with the responders' preferences for female obstetricians/gynecologists: their age and religious status, and the sex of their regular obstetricians/gynecologists. Women who preferred a female obstetrician/gynecologist assigned a lesser weight to the physician's knowledge when choosing them. Older and religious women as well as those who attributed less weight to the physician's professional knowledge were more likely to prefer a female obstetrician/gynecologist. CONCLUSIONS: The majority of responders to our survey (Israeli Druze women), like those in other communities where religiousness and modesty are deeply rooted, prefer female obstetricians/gynecologists, with the overwhelming reasons given being feeling more comfortable and less embarrassed with females, and the notion that female obstetricians/gynecologists are more gentle during intimate procedures.

Cabergoline for reducing ovarian hyperstimulation syndrome in assisted reproductive technology treatment cycles. A prospective randomized controlled trial.

OBJECTIVE: To investigate whether cabergoline (Cb2), a dopamine agonist, reduces ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing assisted reproductive technology (ART), and to analyze whether cabergoline affects the outcome of ART. STUDY DESIGN: Forty infertile women at risk of developing OHSS were enrolled in the trial. The inclusion criteria were as follows: infertile women undergoing IVF with serum estradiol concentration > 4,000 pg/mL or with > 20 follicles > 12 mm on the day of human chorionic gonadotropin (hCG) administration, and 18-40 years of age. They were randomized into 2 groups: the Cb2 group (n = 20) received 0.5 mg oral Cb2 per day for 8 consecutive days beginning on the day of hCG, and the control group (n = 20) received no medication. RESULTS: Ascites was significantly lower (p = 0.008) in the Cb2 group as compared with the control group. The incidence of moderate OHSS was also significantly lower (p = 0.04) in the Cb2 as compared to the control group. There was no evidence of statistically significant differences regarding the parameters of ART outcome. CONCLUSION: Our data supports the use of Cb2 in the management of high-risk women undergoing ART and, consequently, achieving lowered risk of OHSS, with no deleterious impact on ART outcomes.

Obstetricians and gynecologists: which characteristics do Israeli lesbians prefer?

AIM: The aim of this study was to explore lesbians' preferences when choosing obstetricians/gynecologists. MATERIAL AND METHODS: This cross-sectional study included 100 lesbian and 100 heterosexual women. A 40-item questionnaire assessed the correlation between a patient's sexual identity and her specific preferences for obstetricians/gynecologists. RESULTS: The top five most important parameters for both groups in choosing obstetricians/gynecologists overlapped greatly. Four of those were experience, ability, knowledge and personality. Only one parameter differed: lesbians ranked 'sexually tolerant' as the third most important characteristic while heterosexuals ranked 'availability' as the fifth most important characteristic. Lesbians rated 'sexual tolerance' significantly higher than heterosexuals (P < 0.001). More lesbians (56%) preferred female obstetricians/gynecologists compared to heterosexuals (21%) (P < 0.001). When compared to heterosexuals, more lesbians preferred female obstetricians/gynecologists for intimate and non-intimate procedures (P < 0.001). But within the lesbian population, a higher percentage of subjects showed a preference for female obstetricians/gynecologists only for intimate procedures. Lesbians used the following to describe their preference for female obstetricians/gynecologists: feeling more comfortable; gentle; sympathetic; patient; more understanding of women's health; better physicians in general; and more sexually tolerant (P < 0.001 vs heterosexual). However, when we looked only at the lesbian population, the majority did not exhibit a preference for a female obstetrician/gynecologist for any of these reasons. The main reason given by the 56% of the lesbians who said they prefer female obstetricians/gynecologists was feeling more comfortable. CONCLUSION: Overwhelmingly lesbians prefer sexually tolerant obstetricians/gynecologists regardless of their gender; however, only a small number of lesbian subjects in this study considered their obstetricians/gynecologists as displaying this characteristic.

Embryo quality in controlled ovarian stimulation for in vitro fertilization in young poor responders.

This retrospective matched case control study was conducted to evaluate the effects of poor ovarian response in a group of young women (20-30 years) on embryos quality in controlled ovarian hyperstimulation (COH) for in vitro fertilization. Thirty-nine young patients with poor ovarian response (≤5 oocytes on retrieval) were enrolled and compared to age- and date-matched controls. Maximal Estradiol levels, number of oocytes aspirated, number of M2 oocytes and number of fertilized oocytes were significantly lower in the study group compared to controls. Implantation rate and rate of good quality embryos transferred of the study group and control were comparable (15.3 versus 16.3% and 62 versus 67.2%, respectively). Additionally, clinical pregnancy rate per transfer and delivery rate per transfer were also comparable (26.6 versus 35.8% and 23.3 versus 30.7%, respectively). The rate of cycles with no transfer, however, was 23.07% in the study group compared to zero cycles with no transfer in the control group. We conclude that young poor responders may still have reasonable proportion of good quality embryos when compared to controls. This results in comparable implantation rate and clinical pregnancy rate. Cycle transfer cancelation, however, represents a true barrier for achieving pregnancy.

Total fertilization failure in intra-cytoplasmic sperm injection cycles--classification and management.

In this retrospective cohort study we intended to propose a classification and preliminary management strategy for couples exhibiting total fertilization failure (TFF) in intra-cytoplasmic sperm injection (ICSI) cycles. Sixteen couples with a total of 27 cycles exhibiting TFF, age <40 and/or more than four M2 oocytes aspirated were enrolled. While TFF occurred in 4.3% of all 3723 ICSI cycles, in women younger than 40 with at least 5 M2 oocytes the TFF rate was 0.7%. Indications for ICSI were severe male factor and unexplained infertility. Of the 16 couples with TFF, 4 demonstrated a single episode of TFF, with either subsequent or former normal fertilizations, thus implying possible sporadic faulty laboratory conditions. Ten couples demonstrated repeated total or very low fertilization rates, hinting at a gamete defect not overcome by ICSI. Two couples experienced TFF in the first and only cycle performed at our unit. We conclude that initial and repeated TFF hints at severe gamete defects for which only donor gametes may prove successful while sporadic TFF events could simply imply a technical modifiable condition.

Genomic analysis of hESC pedigrees identifies de novo mutations and enables determination of the timing and origin of mutational events.

Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs.

Psychological response and cortisol reactivity to in vitro fertilization treatment in women with a lifetime anxiety or unipolar mood disorder diagnosis.

OBJECTIVE: Knowledge regarding the emotional and physiologic response of women with psychiatric disorders undergoing in vitro fertilization (IVF) treatments is rather limited. We evaluated psychological adjustment and cortisol reactivity to IVF treatment in women with a lifetime diagnosis of a unipolar mood or anxiety disorder compared to those without such a diagnosis. METHOD: Women undergoing IVF treatments (N = 121) were interviewed from January 2006 to December 2007 to assess for the presence of a history of a lifetime DSM-IV-TR unipolar mood or anxiety disorder. They were evaluated prospectively at baseline, at ovulation, and before the pregnancy test. Primary outcome measures included assessments of depressive and anxiety symptoms (Center for Epidemiologic Studies Depression Scale and State-Trait Anxiety Inventory, respectively) and plasma cortisol levels. RESULTS: Of 108 participants included in the study, 19.4% (n = 21) were determined to have a lifetime Axis I unipolar mood or anxiety diagnosis. Women with lifetime Axis I psychopathology showed significantly greater symptom elevation for depression (F2,194 = 10.97, P < .001) and for anxiety (F2,194 = 3.4813, P = .033) compared to the group without psychopathology. A different physiologic pattern was observed for cortisol response: whereas the group without psychopathology responded physiologically to the stressful treatment with continuously elevated cortisol levels, a blunted cortisol response was observed for the group with lifetime psychopathology (F2,200 = 2.9, P = .05). CONCLUSIONS: Women diagnosed with a lifetime unipolar mood or anxiety disorder developed robust symptom exacerbation during IVF treatment compared to women without an Axis I diagnosis. Conversely, the women with a lifetime diagnosis are characterized by a blunted cortisol response, indicating a pattern of dissociation between the robust increase in anxiety and depression and cortisol response to the acute psychological stress. This study emphasizes the need for a psychiatric screening prior to IVF treatment and for the utilization of preventive psychiatric and psychological interventions.

[Anti mullerian hormone (AMH)--is it a new reliable marker of the ovarian reserve? Its role in predicting the ovarian response in assisted reproductive technology (ART)].

Anti-Müllerian hormone (AMH) is predominantly known for its important role in the differentiation of the male and female sexual system during the early embryonic period. Recently, many animal and human researches have been studying the role of the AMH in the postnatal ovarian function. In the female, AMH is produced by the granulosa cells of early developing follicles. It plays a major role in the folliculogenesis and seems to be able to inhibit the initiation of the growth of primordial follicles and FSH-induced follicles. As AMH is expressed throughout the folliculogenesis, from the primary follicular stage to the antral stage, the serum levels of AMH may represent both the quantity and the quality of ovarian follicles. Thus, the AMH levels may be useful as a new potential marker of the ovarian reserve. As compared to other ovarian reserve tests, the AMH has unique characteristics which make it a favorable marker. The measurement of AMH levels may be useful in the prediction of poor response and cycle cancellation as well as hyper-response and the ovarian hyperstimulation syndrome in assisted reproductive technology (ART). We assume that the measurement of AMH Levels may play a role in the individualization of treatment strategies among patients who are treated by ART. However, the AMH cannot predict the qualitative ovarian response in ART. In men, the AMH was not found to have satisfactory clinical utility as a single marker of spermatogenesis.

Genetic and physiological study of morphologically abnormal human zona pellucida.

OBJECTIVE: To investigate genetic, molecular and functional aspects of human zona pellucida (ZP) in oocytes with an abnormal appearance. STUDY DESIGN: The study included three women with unexplained infertility whose oocytes had an abnormal ZP appearance and the mother and fertile sister of one of them. The coding exons and their flanking intron regions of the four ZP genes and the regulatory element for the ZP3 gene were sequenced. Immunofluorescence staining of discarded oocytes using monoclonal antibodies against recombinant human ZP glycoproteins and a hemizona assay were performed. RESULTS: No new mutations were observed in the ZP1 (12 exons), ZP2 (19 exons), ZP3 (9 exons), ZP4 (12 exons) genes or in the ZP3 regulatory element of the three studied women. Sequencing of the genes revealed eight synonymous and non-synonymous reported polymorphisms only in ZP1, ZP2 and ZP3. Immunofluorescence staining of the discarded oocytes of two women showed clear and strong staining of the ZP1, ZP2 and ZP4 proteins, but weak staining of the ZP3 protein, although their ZP displayed normal sperm binding ability in the hemizona assay. Intracytoplasmic sperm injection yielded good pregnancy outcomes, even though few injected oocytes developed normally up to day 3. CONCLUSIONS: The abnormal oocyte ZP appearance in the three study women may not have been due to the genetic changes in the ZP genes. Moreover, sperm binding was normal despite low ZP3 staining observed, suggesting that ZP3 profile may play a subordinate role in the reported cases. Our findings support previous studies which claim that abnormal oocyte morphology is not associated with a decrease in fertilization rates or birth outcomes in couples undergoing intracytoplasmic sperm injection.

Effects of cancer on ovarian response in controlled ovarian stimulation for fertility preservation.

OBJECTIVE: To evaluate the effects of cancer on ovarian response in controlled ovarian hyperstimulation (COH). DESIGN: Retrospective analysis study. SETTING: University-based tertiary medical center. PATIENT(S): 81 cancer patients undergoing controlled ovarian stimulation cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male factor infertility. INTERVENTION(S): Controlled ovarian hyperstimulation and oocytes retrieval. MAIN OUTCOME MEASURE(S): Maximal estradiol levels at day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of dominant follicles, number of oocytes retrieved, and rate of metaphase 2 oocytes. RESULT(S): The overall number of dominant follicles and the number of oocytes aspirated of the study group and control were comparable (8.8 ± 5.3 vs. 9.7 ± 4.9, and 11.93 ± 8.3 vs. 12.3 ± 7.9, respectively). The total dose of gonadotropins used and number of stimulation days of the study group (2,250 IU [1,800-3,000 IU] and 9.5 [8-11]) were also similar to the controls (2,100 IU [1,700-2,900] and 10 [9-13]). Comparison between four subgroups of cancer-breast cancer, soft tissue sarcoma, hematologic malignancies, and gastrointestinal tract cancers-showed no difference in their ovarian response indexes. Regression analysis to assess the effect of cancer on ovarian response showed no effect on the main outcome measured. CONCLUSION(S): Cancer does not influence ovarian response in COH for fertility preservation.

An embryo cleavage pattern based on the relative blastomere size as a function of cell number for predicting implantation outcome.

OBJECTIVE: To analyze whether the cleavage pattern redefined for all cleavage stages according to the relative blastomere size as a function of cell number has an additive value in predicting implantation potential of day-2 and day-3 embryos. DESIGN: Retrospective analysis of standard embryo morphologic parameters (cleavage rate and degree of fragmentation) supplemented by cleavage pattern findings of 347 implanted embryos compared with those of a matched control group of 307 embryos that failed to implant. SETTING: University-based tertiary medical center. PATIENT(S): Two hundred and nine women with successful implantation and 181 controls matched for age and demographic parameters with failed implantation. INTERVENTION(S): In vitro fertilization (IVF), embryo assessment, and embryo transfer. MAIN OUTCOME MEASURE(S): Determination of cleavage patterns in synchronized and unsynchronized cleaving embryos and correlations with implantation outcomes. RESULT(S): Statistically significantly more embryos of the implanted group had good cleavage patterns compared with the failed implantation group (88% vs. 70%). A good cleavage pattern predicted implantation outcome even for nonsynchronized cleaving blastomeres at three, five, six, and seven cells (79% vs. 59%). Regression analysis demonstrated that adding cleavage pattern to the scoring system increased our ability to predict implantation in the training set; the area under the curve was the highest (0.707) as was the proportion of correct classification (>70%) when the cleavage pattern was assessed on both days 2 and 3. CONCLUSION(S): When combined with measurements of the cleavage rate and degree of fragmentation, the cleavage pattern refines our ability to predict the likelihood of implantation, representing a definitive tool in the selection of top-quality embryos.

Successful pregnancy following transfer of frozen-thawed embryos in a patient with pseudomyxoma peritonei who underwent peritonectomy and bilateral oophorectomy.

Pseudomyxoma peritonei is a rare, chronic relapsing disease in which tumor cells in the abdomen produce excessive mucin with a significant mortality rate. We describe a young unmarried nulligrava who underwent fertility preservation by in vitro fertilisation and embryo cryopreservation prior to radical surgery and adjuvant chemotherapy. Pregnancy was achieved, although complicated by obstructive uropathy. She delivered a healthy infant at 32 weeks' gestation. The few descriptions of fertility and pregnancy outcome in pseudomyxoma peritonei that appear in the literature are reviewed.