Luteal phase support with GnRH agonist does not eliminate the risk for ovarian hyperstimulation syndrome.

This study aims to report a case of early, severe ovarian hyperstimulation syndrome (OHSS) following GnRH agonist trigger for final oocyte maturation despite luteal support with a GnRH agonist. Contrary to the claim that luteal support using a GnRH agonist eliminates the risk for OHSS in high-risk patients, this report alerts practitioners to the risk of severe OHSS development despite GnRH agonist luteal support in patients receiving GnRH antagonist protocol with GnRH agonist triggering and cautions the practitioners to consider other measures of OHSS prevention.

Trends in primeval ß-hCG level increment after fresh and frozen-thawed IVF embryo transfer cycles.

Mid-trimester beta-human chorionic gonadotropin (BHCG) levels are considerably higher in pregnancies resulting from frozen embryo transfer (FET) compared with fresh (FRET), leading to a higher false positive rate in aneuploidy screening tests. We aimed to investigate the dynamics of BHCG increment and its predictive value for cycle outcome. A retrospective analysis of FRET and FET cycles. BHCG values on days 14 and 16 post embryo transfer were compared and stratified according to the number of sacs demonstrated on US scan at six weeks gestation, and pregnancy outcome (biochemical pregnancy, ectopic pregnancy, spontaneous abortion, and a singleton or twin birth). A prediction model for live birth was built. A total of 430 treatment cycles were analyzed. The average BHCG levels were significantly higher in FET compared with FRET group in nonviable pregnancies on day 14, 450 vs. 183 IU/L, p < .05 and day 16, 348 vs. 735 IU/L, p < .05, respectively. The increment of BHCG was significantly steeper in the FET compared with FRET group in biochemical pregnancies (F = 6.485, p = .012*). Optimal cutoff level for live birth prediction in the FRET group was 211 IU/L (sensitivity 84%, specificity 76.2%) for day 14 and 440 IU/L (sensitivity 86.0% and specificity 72.5%) for day 16. The increment in BHCG differed significantly between the FRET and FET cycles in nonviable pregnancies. Nevertheless, the difference in BHCG levels observed in the second trimester in pregnancies conceived after FRET and FET cycle may begin as early as the fourth week of pregnancy.

Acute Myeloid Leukemia Affects Mouse Sperm Parameters, Spontaneous Acrosome Reaction, and Fertility Capacity.

Leukemia is one of the most common cancers in patients of reproductive age. It is well known that chemotherapy, used as anti-cancer therapy, adversely affects male fertility. Moreover, the negative effect of leukemia on sperm quality, even before chemotherapy treatment, has been reported. However, the mechanisms behind this disease's effect on sperm quality remains unknown. In this study, we examine the direct effect of leukemia and chemotherapy alone and in combination on sperm parameters and male fertility. For this, we developed an acute myeloid leukemia (AML) mouse model (mice were treated with AML cells C1498 and developed leukemia); these mice then received cytarabine chemotherapy. Our findings reveal a significant reduction in sperm concentration and motility and a significant increase in abnormal morphology and spontaneous acrosome reaction of the sperm following AML and chemotherapy treatment, alone and in combination. We also found a reduction in male fertility and the number of delivered offspring. Our results support previous findings that AML impairs sperm parameters and show for the first time that AML increases spontaneous acrosome reaction and decreases male fertility capacity and number of offspring.

Does progesterone to oocyte index have a predictive value for IVF outcome? A retrospective cohort and review of the literature.

The potential adverse effect of Serum progesterone (SP) elevation on the day of hCG administration is a matter of continued debate. Our study aimed to evaluate the relative value of progesterone to a number of aspirated oocytes ratio (POI) to predict clinical pregnancy (CP) and live birth (LB) in fresh IVF cycles and to review the relevant literature. A retrospective analysis of GnRH Antagonist IVF-ET cycles. POI was calculated by dividing the SP on the day of hCG by the number of aspirated mature oocytes. A multivariate logistic regression analysis was performed to evaluate the predictive value of POI for CP and LB. Cycle outcome parameters included clinical pregnancy, live-birth and miscarriage. A total of 2,693 IVF/ICSI cycles were analyzed. POI was inversely associated with CP adjusted OR 0.063 (95% CI 0.016-0.249, p < .001) and with LB adjusted OR 0.036 (95% CI 0.007-0.199, p < .001). For prediction of LB, the area under the curve (AUC) was 0.68 (95% CI 0.64-0.71, p < .001) for the POI model. POI above the 90th percentile with a value of 0.36 ng/mL/oocyte results in CP and LB rates of 8.0 and 5.9%, respectively. POI is a simple index for the prediction of IVF-ET cycle outcomes, it can advocate a limit above which embryo transfer should be reconsidered.

The reproductive potential of patients with Mayer-Rokitansky-Küster-Hauser syndrome using gestational surrogacy: a systematic review.

Women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome may reproduce after uterine transplantation or IVF using a gestational surrogate. As uterine transplantation is still an experimental procedure, data on their clinical outcome using assisted reproduction techniques are imperative to allow evidence-based counselling. For this purpose, a systematic non-restricted electronic literature search was conducted. The 14 studies included in this review were published between 1988 and 2011. From a cohort of 140 patients with MRKH syndrome, mostly from the the USA and Israel, only four studies contained data on more than 10 patients; the others were case reports or small series. In the studies reviewed, 125 patients underwent 369 cycles of IVF with gestational surrogacy, and delivered 71 newborns. The reporting of outcome of patients with MRKH syndrome undergoing assisted reproduction techniques in the available literature is less than optimal and is characterized by bias of publication, inconsistent reports, including few patients, treated over a long time span, and lacking systematic reports from large IVF centres. None of the national registries contain specific outcome data on patients with MRKH syndrome. The paucity of data limits the possibility to draw firm conclusions but substantiates the need for a systematic multicentre reporting system.

[CLINICAL ASPECTS OF INTRAUTERINE INSEMINATION].

INTRODUCTION: Intrauterine insemination (IUI) is an intervention performed frequently in the treatment of couples suffering from subfertility and women treated using donor sperm. The factors predicting its success include female parameters such as age and ovarian function and male parameters such as sperm quality. However, many details regarding its clinical application such as the methodology of sperm preparation, timing of IUI, the number of inseminations in the same cycle, the recommended number of cycles to be performed and the minimal threshold values of the sperm sample profile required are controversial. The conclusion to be drawn from this literature survey is that there is still lack of sufficient good quality studies performed to allow evidence based recommendations for the performance of IUI.

The effect of two distinct levels of oxygen concentration on embryo development in a sibling oocyte study.

PURPOSE: This prospective randomized study used sibling oocytes of 258 women with ≥8 oocytes to compare the effect of 5 % O(2) versus 20 % O(2) concentrations on embryo development and clinical outcome. METHODS: Oocytes of each case were divided between incubators with either 5 % or 20 % O(2) concentration. Outcome measures were fertilization, cleavage, embryo quality, blastocyst formation, and implantation, pregnancy and live birth rates. RESULTS: Fertilization and cleavage rates were similar in both groups. The 5 % O(2) group had significantly more blastomeres (P < 0.05) and more top-quality embryos on day 3 (P < 0.02), as well as significantly more available embryos for transfer (31.6 % vs. 23.1 % for the 20 % O(2) group; P < 0.0001). There were significantly more cycles with good embryos in the 5 % group (76/258) than in the 20 % group (38/258) (P < 0.0001). Implantation and pregnancy rates were significantly higher for 5 % O(2) embryos (P < 0.03 and P < 0.05, respectively). Live birth rates per embryo transfer were 34.2 % and 15.8 %, respectively, P < 0.05. CONCLUSIONS: Implantation, pregnancy and live birth rates are higher, and more good quality embryos are available for transfer and freezing with reduced rather than with atmospheric oxygen concentrations during embryo incubation.

Conventional IVF versus ICSI in sibling oocytes from couples with endometriosis and normozoospermic semen.

PURPOSE: This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with endometriosis and normozoospermic semen during IVF cycles. METHODS: Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Rates of fertilization, cleavage, blastulation and embryonic morphology were assessed. RESULTS: A total of 786 sibling cumulus-oocyte complexes (COC) were randomized between insemination by conventional IVF (387 COC) or ICSI (399 COC). A significantly higher fertilization rate was found in the ICSI group (ICSI versus IVF, 73.3±23 % versus 54.7±31.9 % respectively; P=0.003), yielding a higher mean number of day 2 embryos (5.2±3.4 versus 3.6±2.9 respectively; P=0.002). Triploid fertilization rate (3PN/COC) was significantly higher in the IVF group compared to the ICSI group (3.9±8.7 % versus 0.9±3.1 % respectively; P=0.02). The morphology score and rate of development of day 2 and 3 embryos were not different between the two groups. Comparison of embryo transfer cycles in which either IVF or ICSI only embryos were transferred did not reveal any statistically significant differences in pregnancy or implantation rates. CONCLUSION: ICSI appears to be a better treatment option than conventional IVF in endometriosis-associated infertility, since it offers the advantages of higher fertilization rate and mean number of embryos and lower rate of total fertilization failure and triploid fertilization.

The Challenges and Hopes in Treating Patients with NOA.

Infertility due to the male factor occurs in no less than 50% of investigated couples [...].

Is there any truth in the myth that IVF treatments involve weight gain?

Purpose: To examine body weight change in women undergoing in vitro fertilization and embryo transfer (IVF-ET) using antagonist protocol after up to three treatment cycles. Methods: A prospective cohort study among IVF patients treated between 2018 and 2019. Each patient underwent weight measurement three times during the treatment cycle: before treatment, at the beginning of the hormonal stimulation, and at the completion of the cycle, on the day of the pregnancy test. Data were also analyzed according to the body mass index (BMI) groups for normal weight, overweight, and obese patients. Finally, weight changes were recorded following altogether 519 treatment cycles, 240, 131, and 148 cycles, for normal weight, overweight, and obese patients, respectively. Results: The change in the patient's weight was clinically non-significant either during the waiting period or during gonadotropin administration, and overall, during the first, second, or third treatment cycles. The recorded mean total weight change of 0.26 ± 1.85, 0.4 ± 1.81, and 0.17 ± 1.7, after the first, second, or third treatment cycles, represent a change of 0.36%, 0.56%, and 0.23% of their initial weights, respectively. This change of less than 1% of the body weight falls short of the clinically significant weight gain of 5%-7%. Analyzing the data for the various BMI groups, the changes observed in body weight were under 1%, hence with no clinical significance. Conclusion: The findings of the study reject the myth that hormone therapy involves clinically significant weight gain, and this can lower the concerns of many patients who are candidates for treatment of assisted reproductive technology.

Computerized cell-scanning system for evaluating human spermatogenesis in non-obstructive azoospermic patients.

There may be incompatibility between testicular histopathological evaluation and testicular sperm extraction (TESE) outcome. Assessment for sperm presence and different pathological disturbances of non-obstructive azoospermia (NOA) remains challenging. An assay for maximal sampling and accurate identification of testicular cells from NOA patients undergoing TESE and autopsied fertile controls was developed. Testicular cells stained and scanned automatically for morphology underwent fluorescence in-situ hybridization using centromeric probes for chromosomes X, Y and 18 after destaining. Cells were automatically classified according to ploidy, and ratios of haploid cells and autosomal (18) and sex-chromosome bivalent rates were calculated. Identification of testicular cells in suspension enabled prediction of spermatogenesis in seven of eight Sertoli-cell-only syndrome patients. Haploid/diploid cell ratios were 67.6:32.2 for controls and 9.6:90.4 for patients. Both autosomal (18) and sex-chromosome bivalents were present in patients (4.1 ± 5.82%) and controls (19.7 ± 8.95%). Few tetraploid pachytene spermatocytes were observed. More secondary spermatocytes with NOA showed two distinct signals for chromosome 18 (27.9 ± 32.69%) compared with controls (0.4 ± 0.35%). The computerized cell-scanning system enables simultaneous application of morphology and chromosome analysis of testicular cells, which enhance assessing different pathological disturbances and estimating the likelihood of a successful second TESE procedure.

Do spontaneously decreasing estradiol levels prior to triggering of ovulation adversely impact in vitro fertilization outcomes?

OBJECTIVE: The aim of this study was to explore the potential adverse effect of spontaneously decreasing serum estradiol (SE) levels on in vitro fertilization (IVF) outcomes. METHODS: This retrospective single-subject study analyzed IVF cycles conducted at a hospital IVF unit between 2010 and 2017. Overall, 2,417 cycles were analyzed. Only cycles with spontaneously decreasing SE before human chorionic gonadotropin (hCG) triggering were included. Each patient served as her own control, and subsequent cycles were analyzed for recurrent SE decreases. The main outcome was the number of oocytes retrieved. RESULTS: Cycle characteristics were similar between the study (SE decrease) and control groups, with the exception of the median SE on the day of hCG triggering (899.7 pg/mL; interquartile range [IQR], 193-2,116 pg/mL vs. 1,566.8 pg/mL; IQR, 249-2,970 pg/mL; p< 0.001). The study group, relative to the control group, had significantly fewer total oocytes (5 [IQR, 2-9] vs. 7 [IQR, 3-11]; p= 0.002) and significantly fewer metaphase II (MII) oocytes (3 [IQR, 1-6] vs. 4 [IQR, 2-8]; p= 0.001) retrieved. The study group had fewer cleavage-stage embryos than the control cycles (3 [IQR, 1-6] vs. 4 [IQR, 2-7]; p= 0.012). Compared to cycles with a ≤ 20% SE decrease, cycles with a > 20% decrease had significantly fewer total and MII oocytes retrieved. SE decrease recurred in 12% of patients. CONCLUSION: A spontaneous decrease in SE levels adversely affected IVF outcomes, with a linear correlation between the percentage decrease and the number of oocytes retrieved. SE decrease can repeat in later cycles.

Patients' Evaluation of Intervention by a Medical Clown Visit or by Viewing a Humorous Film Following In Vitro Fertilization and Embryo Transfer.

This study compared responses to an in-person clown visit and a humorous film following in vitro fertilization and embryo transfer. Intervention was a 10-minute clown visit (n = 101) or 10-minute humorous video clip (n = 99). Demographic and fertility-related data and preintervention anxiety scores were collected. Participants completed an Evaluation of Intervention form postintervention. There were no group differences on demographic or fertility-related data or anxiety scores. Findings indicate while participants viewed the intervention positively, the clown visit offered a higher degree of satisfaction in more patients than did the film. Median evaluation scores were significantly higher for the clown visit, specifically reducing anxiety level and being more distracting. Both groups reported that the exposure made the clinic experience more pleasant and did not bother them, and most would recommend incorporating the intervention in routine treatment. However, free-text comments clearly expressed greater enthusiasm to the in-person clown intervention than to the film.

The midluteal decline in serum estradiol levels is drastic but not deleterious for implantation after in vitro fertilization and embryo transfer in patients with normal or high responses.

OBJECTIVE: To determine the impact of the peak E(2) level and its midluteal decline on IVF-ET outcome in a group of normal- and high-responding patients. DESIGN: Retrospective analysis of IVF-ET data. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENT(S): A total of 100 patients aged 98% E(2) decline; however, the difference did not reach statistical significance. CONCLUSION(S): Multifactorial analysis refutes the negative role of supraphysiologic levels of E(2) on the day of hCG administration or its dramatic decline at the midluteal phase on the success rate after embryo transfer. A possibly increased rate of early spontaneous abortion in the high-response group warrants further verification.

Increased frequency of female partner chromosomal abnormalities in patients with high-order implantation failure after in vitro fertilization.

OBJECTIVE: To find the type and frequency of chromosomal abnormalities in a selected group of high-order implantation failure (> or =6 IVF trials and > or =15 transferred embryos) and to evaluate its impact on pregnancy outcome. DESIGN: A retrospective study. SETTING: In vitro fertilization (IVF) unit in a university affiliated hospital. PATIENT(S): Sixty-five couples with high-order implantation failure in IVF and embryo transfer. INTERVENTION(S): In vitro fertilization/embryo transfer (ET), work-up for implantation failure, cytogenetic analysis of the couple. MAIN OUTCOME MEASURE(S): We studied the type and frequency of chromosomal changes, quality of embryos, cumulative pregnancy rates, and pregnancy outcome. RESULT(S): The mean number of treatment cycles per patient, before karyotyping was 7.8 +/- 2.4 (range: 6 to 16 cycles). The mean cumulative number of all transferred embryos per patient was 25.7 +/- 10.3 (range: 9 to 65 embryos). Chromosomal abnormalities were found in 10 of 65 (15.4%) cases: translocations in six, mosaicism in two, and inversion or deletion in another two. The morphologic characteristics of the transferred embryos and the cumulative pregnancy rates were similar in patients with implantation failure with and without chromosomal changes. Three of the 16 patients with abnormal karyotype delivered and three miscarried within a follow-up period of 1 year. CONCLUSION(S): A high frequency of chromosomal aberrations was found in a selected group of high-order implantation failures, a similar frequency to recurrent miscarriages. Karyotyping is recommended as part of the work-up for repeated implantation failure in assisted reproduction. Treatment options include further IVF trials, preimplantation genetic diagnosis, or oocyte donation, tailored according to the type of chromosomal change. An international registry should be considered to assist in counseling these patients.

Ovarian pregnancy-a 12-year experience of 19 cases in one institution.

OBJECTIVES: To report the prevalence, presentation, diagnostic modalities, and treatment of ovarian pregnancy in one institution. STUDY DESIGN: Retrospective case control study of 19 cases of ovarian pregnancy treated between 1990 and 2001 at Assaf Harofeh Medical Center, Zerifin, Israel. MAIN OUTCOME MEASURES: Prevalence, presentation, diagnostic modalities, surgical treatment, and relation to intrauterine device (IUD) use. RESULTS: Nineteen ovarian pregnancies, diagnosed between 1990 and 2001, comprised (19/694) 2.7% of all ectopic pregnancies, 1:3000 of all live births leading to a mean ovarian pregnancy per year of 1.6. Presenting symptoms were similar to those of tubal pregnancies including circulatory collapse which was present in 4/19 (21%) of patients. Culdocentesis for diagnostic purposes, has become an unnecessary procedure. Wedge resection by laparotomy was the treatment of choice in the past, and from 1994, it was performed exclusively by laparoscopy. When an ovarian pregnancy was diagnosed, intrauterine device was present in 68% of the patients and in 76% of the fertile women. CONCLUSIONS: The absolute number of ovarian pregnancies between 1900 and 2001 increased but the prevalence rate per delivery was stable. Despite modern diagnostic modalities patients still present in circulatory collapse-conservative approach may underestimate the potential risk of bleeding. Culdocentesis has no clinical diagnostic benefits. Laparoscopy is invaluable, as diagnosis and treatment can be carried out as a single treatment. Laparoscopic wedge resection is the treatment of choice. The relation between IUD use and ovarian pregnancies is still strong.

Hormonal regulation of pigment epithelium-derived factor (PEDF) expression in the endometrium.

Pigment epithelium-derived factor (PEDF) is highly expressed in the female reproductive system and is subjected to regulation by steroid hormones in the ovary. As the uterine endometrium exhibits morphological and functional changes in response to estrogen (E2) and progesterone (P4), we aimed at characterizing the expression of PEDF in this component of the female reproductive tract and further at exploring the hormonal regulation of its expression. We found that PEDF is expressed in human and mouse endometrium. We further showed that this expression is subjected to regulation by steroid hormones, both in vivo and in vitro, as follows: E2 decreased PEDF expression and P4 increased its levels. In human endometrial samples, PEDF levels were dynamically altered along the menstrual cycle; they were low at the proliferative and early secretory phases and significantly higher at the late secretory phase. The expression levels of PEDF were inversely correlated to that of vascular endothelial growth factor (VEGF). We also showed that PEDF receptor was expressed in the endometrium and that its stimulation reduced VEGF expression. Illustrating the pattern of PEDF expression during the menstrual cycle may contribute to our understanding of the endometrial complexity.

Intracytoplasmic sperm injection outcome of ejaculated versus extracted testicular spermatozoa in cryptozoospermic men.

OBJECTIVE: To compare intracytoplasmic sperm injection (ICSI) outcome of patients with cryptozoospermia after use of ejaculated versus testicular sperm in different cycles of the same patients. DESIGN: Retrospective cohort study. SETTING: University-affiliated infertility center. PATIENT(S): A total of 17 patients with cryptozoospermia who underwent a total of 116 ICSI cycles. INTERVENTION(S): The patients initially underwent several ICSI cycles using ejaculated sperm (n = 68, 58.6%) that were followed by ICSI cycles using testicular sperm (n = 48, 41.4%). MAIN OUTCOME MEASURE(S): Fertilization rate, pregnancy rate (PR). RESULT(S): There were no significant differences in fertilization rates between the two subgroups. A comparison between testicular sperm extraction (TESE) versus ejaculated sperm cycles revealed significantly higher implantation rate (20.7% vs. 5.7%), higher PR (42.5% vs. 15.1%), and higher take home baby rate (27.5% vs. 9.4%). A multivariable logistic regression analysis showed three significant predictors for pregnancy, namely the use of testicular sperm (odds ratio [OR] 5.1, 95% confidence interval [95% CI] 1.8-14.8), use of motile sperm (OR 12.9, 95% CI 2.1-79.1), and female age (OR 0.83, 95% CI 0.7-0.9). CONCLUSION(S): Testicular sperm extraction is justified in patients with cryptozoospermia who fail to conceive by ICSI using ejaculated spermatozoa, as it offers higher PR.

Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the current available data regarding ovarian performance of patients diagnosed with malignant disease undergoing controlled ovarian hyperstimulation (COH) for fertility preservation, before radio/chemotherapy, compared with age-matched, healthy patients undergoing COH for in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). DESIGN: Meta-analysis of the data available from a systematic review of the literature. SETTING: Academic centers of infertility and IVF. PATIENT(S): Patients with malignant disease, before radio/chemotherapy, undergoing COH for fertility preservation within comparative studies with healthy, age-matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peak estradiol levels on day of human chorionic gonadotropin administration, number of oocytes retrieved, fertilization rate, incidence of low ovarian response, and cycle cancellation. RESULT(S): Only seven retrospective, case-controlled studies were found to match our objective. Overall, the results of the meta-analysis indicate that the number of retrieved oocytes rate was statistically significantly lower compared with age-matched healthy IVF patients. The incidence of poor ovarian performance and risk of cycle cancellation as well as the calculated number of two pronuclei zygotes achieved among patients with cancer were comparable with their age-matched controls. CONCLUSION(S): Women with malignant disease should expect a lower number of oocytes retrieved after COH for fertility preservation, compared with healthy, age-matched patients. Presently, there is paucity of evidence to assess the effect of a specific malignant disease on ovarian response to COH before IVF for fertility preservation. Multicentric studies should be conducted to resolve these important issues.