Ariel Weissman

Poor outcome with round spermatid injection in azoospermic patients with maturation arrest

OBJECTIVEnTo compare the outcome of intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI), both obtained by testicular sperm extraction (TESE), and to compare the results of fresh versus frozen ROSI.nnnDESIGNnRetrospective study.nnnSETTINGnAn IVF unit at a university hospitalPatient(s): Eighteen infertile couples with nonobstructive azoospermia.nnnINTERVENTION(S)nTESE with ROSI or ICSI of mature spermatozoa into metaphase II oocytes was performed. The resulting embryos were transferred to female partners. The spare round spermatids were frozen.nnnMAIN OUTCOME MEASURE(S)nFertilization and cleavage rates, embryo quality, and clinical pregnancy rates.nnnRESULT(S)nSeventeen ROSI cycles and six ICSI cycles were compared. Fertilization rate following ROSI (44.9%) was significantly lower than with ICSI (69%). A significantly higher rate of cleavage arrest occurred following ROSI (40.8%) as compared to ICSI (8.2%). The morphology of embryos resulting from ROSI was significantly poorer. No pregnancies were achieved following ROSI as compared to a 50% clinical pregnancy rate in the ICSI group. The fertilization and cleavage rates following ROSI with fresh versus frozen-thawed spermatids were comparable.nnnCONCLUSION(S)nIn azoospermic patients with maturation arrest at the stage of round spermatids the efficiency of ROSI appears to be extremely poor. The role of ROSI in the treatment of nonobstructive azoospermia should be reevaluated.

Chromosomal mosaicism detected during preimplantation genetic screening: results of a worldwide Web-based survey

Embryonic mosaicism, the presence of more than one distinct cell line within an embryo, has recently become the focus of growing attention and controversy in the context of preimplantation genetic screening (PGS). To evaluate the extent of mosaic aneuploidy in clinical practice and to gain insight on the practices and views regarding this issue, we conducted a survey using a prospective, 20-item Web-based questionnaire with questions related to practices and views regarding mosaicism in PGS. A total of 102 inxa0vitro fertilization (IVF) units from 32 countries that performed 108,900 IVF cycles annually responded to the survey. More than half responded that embryonic mosaic aneuploidy is reported by the laboratory, but 31.9% stated that samples are reported as euploid or aneuploid only. If mosaic aneuploidy is reported, 46% stated that it was present in ≤10% of the embryos. More than two-thirds were of the opinion that next-generation sequencing is required to reliably detect mosaicism. Among centers performing PGS, 47.9% consider embryonic mosaicism when detected in >20% of the cells, and nearly two-thirds believe that mosaic aneuploid embryos should be stored for potential therapeutic use after extensive and appropriate counseling. In summary, mosaicism has always existed in preimplantation embryos, and new technologies can now detect its presence with higher resolution. More studies are needed before definite conclusions can be drawn.

Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com.

PurposeTo identify the leading treatment strategies for infertile women with PCOS on an international scale.MethodsA retrospective evaluation using the results of a web-based survey, (IVF-Worldwide (www.IVF-worldwide.com), posted from 1 to 30 September 2010 was performed. Binomial confidence intervals for proportions were calculated by the modified Wald method with significance defined as Pu2009<u20090.05 using a DataStar software package (DataStar, Waltham, MA, USA). Incomplete surveys were excluded from the analysis.ResultsThe results from 262 centers in 68 nations were obtained. Clomiphene citrate was the clear first choice, 68xa0%, for PCOS treatment in the respondent group. Eighty-eight percent of respondents utilized ultrasound follicular monitoring when conducting ovulation induction with oral medications. A significant (pu2009<u20090.05) proportion of respondents (66xa0%) did use some BMI cutoff beyond which IVF treatment was not offered. The preferred IVF protocols for PCOS patients were gonadotropin releasing hormone (GnRH) antagonist, 46xa0%, and GnRH agonist, 51xa0%. There was heterogeneity of responses observed regarding the management of a patient at very high risk of OHSS.ConclusionsWhile some advances, such as the use of GnRH antagonist regimen in IVF cycles, were relatively underutilized, the survey gives an unfiltered snapshot at the practice patterns of a large number of clinics. Results from this survey may be used by researchers and professional organizations to improve the clinical care of PCOS women suffering with infertility.

Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques

AbstractPurposenTo identify common and varying practice patterns used by in vitro fertilization (IVF) providers from a broadly distributed, worldwide survey. Specific information regarding clinical IVF practices involving the oocyte maturation triggering, oocyte retrieval and embryo transfer was elicited.nMethodsnThis is an internet-based questionnaire study of IVF practices throughout the world. We used 26 multiple choice questions regarding common clinical practices. The data reported are weighted based on the number of IVF cycles performed at the specific IVF center, represented by a single respondent.ResultsSurveys were completed from 359 centers in 71 countries throughout the world. The most common practice patterns (defined as ≥75xa0% of IVF cycles) identified included: use of human chorionic gonadotropin (hCG) for trigger with an antagonist protocol, no routine patient monitoring from hCG trigger to oocyte retrieval, timing oocyte retrieval 34–37xa0h following oocyte maturing trigger, use of a single lumen retrieval needle, no routine tests following oocyte retrieval prior to patient discharge and use of ultrasound assistance with embryo transfer.ConclusionsThis is the largest and most diversely represented survey of specific IVF practices addressing oocyte maturation triggers, oocyte retrieval and embryo transfers. Several uniform practice patterns were identified that can be correlated with evidence-based medicine; however, we identified multiple variable practice patterns which is likely the result of the absence of definitive evidence to guide IVF practitioners. The results of this survey allow IVF providers to compare their specific practice patterns with those of a global diverse population of IVF providers.

Normalization as a Strategy for Maintaining Quality of Life While Coping with Infertility in a Pronatalist Culture

PurposeInfertility could be highly stressful, particularly in a pronatalist culture. We aimed to develop the concept and a measure of normalization (maintaining normal life routines and feeling “normal”) as a strategy that could enable women with infertility maintain their quality of life (QoL) while coping with this condition. We tested its associations with women’s well-being, distress and QoL in Israel, where being childless is socially unacceptable and highly stigmatized.MethodsOne-hundred and eighty Israeli women undergoing infertility treatment at a fertility community clinic filled in questionnaires assessing normalization-related coping strategies, QoL, and psychological adjustment (distress, wellbeing). Eight months later, 55 women conceived; 55 women who had not conceived completed a second questionnaire.ResultsAt baseline, normalization was related to higher QoL and better adjustment. Structural equation modeling showed that QoL was impaired mainly among women who felt different than others, compared, and blamed themselves. Over time, normalization was overall unrelated to conception or to changes in adjustment yet was protective against decrease in well-being among women who already had a child.ConclusionsInfertility is highly stressful in a pronatalist culture like Israel. It requires treatment yet is not disabling. Patients who manage to maintain normal routines and not feel different than other people their age may experience better QoL and psychological adjustment.

Minimizing the Risk of Infection and Bleeding at Trans-Vaginal Ultrasound-Guided Ovum Pick-up: Results of a Prospective Web-Based World-Wide Survey.

ObjectiveThe objective of this study was to identify clinical practices worldwide, which would help in recognizing women at risk of excessive bleeding or of developing pelvic infection following trans-vaginal ovum pick-up (TV-OPU), measures taken to minimize risks and their management.MethodA prospective, web-based questionnaire with distinct questions related to the practice of TV-OPU.ResultsA total of 155 units from 55 countries performing 97,200 IVF cycles annually responded to this web-based survey. A majority (65xa0%) responded that they would routinely carry out full blood count, while 35xa0% performed coagulation profile. Less than a third agreed screening women for vaginal infections. About a third used both sterile water and antiseptic to minimize ascending infection, and 52xa0% used antibiotics for prophylaxis. Doppler ultrasound was routinely used by 20xa0% of clinicians. 73xa0% of the clinicians preferred conservative management as their first line management for patients diagnosed with intra-abdominal bleeding.ConclusionThe study has identified a wide variation in the practices of minimizing infection and bleeding complications. The dearth of good quality evidence may be responsible for the lack of published guidelines, and therefore a lack of consensus on the optimum practice for minimizing the risk of infection and bleeding during TV-OPU.

Preimplantation genetic screening: results of a worldwide web-based survey

Our objective was to evaluate and characterize the extent and patterns of worldwide usage of preimplantation genetic screening (PGS) among the assisted reproductive technique community. A prospective, web-based questionnaire with questions relating to practices of, and views on, PGS was directed to users and non-users of PGS. A total of 386 IVF units from 70 countries conducting 342,600 IVF cycles annually responded to the survey. A total of 77% of respondents routinely carry out PGS in their clinics for a variety of indications: advanced maternal age (27%), recurrent implantation failure (32%) and recurrent pregnancy loss (31%). Few (6%) offer PGS to all their patients. In most cycles (72%), trophectoderm biopsy is carried out and either array-comparative genomic hybridization (59%) or next-generation sequencing (16%) are used for genetic analysis. Only 30% of respondents regard PGS as clearly evidenced-based, and most (84%) believe that more randomized controlled trials are needed to support the use of PGS. Despite ongoing debate and lack of robust evidence, most respondents support the use of PGS, and believe that it may aid in transferring only euploid embryos, thereby reducing miscarriage rates and multiple pregnancies, increasing live birth rates and reducing the risk of aneuploid pregnancies and births.

Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue

We read with interest the paper of Strauss et al. [1] describing a patient that following transplantation of ovarian tissue for fertility preservation, exhibited increased circulating progesterone concentrations during DHEA supplementation. Since the patient was menopausal at the time of transplantation, and had only a small fraction of ovarian tissue transplanted, the authots attributed the increase in progesterone production to an augmented adrenal synthesis of progesterone. n nWe have previousely described [2] a similar phenomenon in patients with diminished ovarian reserve (DOR) undergoing controlled ovarian stimulation (COS) prior to IVF. In a case control study, we compared progesterone levels during the follicular phase in IVF cycles before and during DHEA supplementation in 15 women with DOR who received 75xa0mg of DHEA daily. Progesterone levels on stimulation day 5 (ng/mL) (0.58u2009±u20090.29 vs. 1.54u2009±u20090.49; pu2009<u20090.0001); and on the day of hCG administration (0.75u2009±u20090.31 vs. 1.87u2009±u20090.49; pu2009<u20090.0001) were significantly higher during DHEA treatment. The number of retrieved and fertilized oocytes was similar in both groups. Five patients (33xa0%) had a clinical pregnancy following DHEA supplementation, of whom 2 had spontaneous abortions and 3 delivered healthy newborns. We concluded that DHEA administration during IVF cycles in women with DOR causes a significant elevation of progesterone levels without an apparent deleterious effect on cycle outcome. n nThe mechanism for the observed increase in progesterone levels during DHEA supplementation remains unknown. Altered adrenal and/or ovarian function as well as alterations in steroidogenic pathways that favor progesterone production could all be implicated. In addition, the possibility of cross reaction between DHEA and progesterone in currently available commercial assays should also be explored. More information and further studies are needed in order to increase our understanding of the effects of DHEA supplementation on reproductive function and outcome.

Cumulative pregnancy and live birth rates through assisted reproduction in women 44–45 years of age: is there any hope?

PurposeThe purpose of the study is to calculate the cumulative pregnancy rate and cumulative live birth rate in women undergoing in vitro fertilization (IVF) at ages 44–45.MethodsThe study calculated cumulative live pregnancy rate and cumulative live birth rate of 124 women aged 44 to 45xa0years old who commenced IVF treatment.Main outcome measuresThe main outcome measures are cumulative live pregnancy rate and cumulative live birth rate.ResultsCumulative live pregnancy rates following 1, 2, 3, and 4 cycles were 5.6, 11, 17, and 20%, respectively, with no additional pregnancies in further cycles. Cumulative live birth rates following 1, 2, and 3 cycles were 1.6, 3, and 7%, respectively, with no additional live births in further cycles.ConclusionsThe cumulative pregnancy rate rises during the first 4 cycles and cumulative live birth rate rises during the first 3 cycles, with no additional rise in pregnancies or deliveries thereafter, suggesting that it is futile to offer more than 3 cycles of treatment to 44–45-year-old women.

Endometrial nerve fibre density in patients undergoing IVF: a pilot study

The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. Presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. This prospective pilot study assessed the presence of nerve fibres in endometrium of women undergoing IVF due to various causes and examined the correlation between the presence of nerve fibres and IVF success. A total of 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Correlations between the presence and density of nerve fibres and aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. Presence of nerve fibres was not correlated with cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without correlation to presence of nerve fibres in the endometrium. Nerve fibres were identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. The presence of nerve fibres does not appear to interfere with implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research. The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. The presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. Our aim was to assess the presence of nerve fibres in endometrium of women with various causes of infertility undergoing IVF and to examine the association between the presence of nerve fibres in the endometrium and IVF success. In a prospective study, 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Associations between the presence and density of nerve fibres and the aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. No association was found between the presence of nerve fibres and the cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without association with the presence of nerve fibres in the endometrium. Nerve fibres can be identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. Their presence does not interfere with embryo implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research.