Ovulatory-Based FET Cycles May Achieve Higher Pregnancy Rates in the General Population and among Anovulatory Women.

This study evaluated which endometrial preparation protocol in frozen embryo transfer (FET) cycles provides the best results for polycystic ovarian syndrome (PCOS) patients and the general population. This retrospective study of 634 FET cycles was conducted 2016-2018. Cycles were divided into Group A: Artificial endometrial preparations for FET (aFET; n = 348), Group B: Ovulatory cycle (n = 286) to compare two methods of endometrial preparation for FET. Artificial endometrial preparation with exogenous estrogen and progesterone versus natural ovulation cycles, modified natural cycles using hCG for the final triggering and letrozole-induced ovulation with hCG. Anovulatory patients were analyzed separately. Anovulatory PCOS patients had significantly higher pregnancy rates with letrozole treatment compared with aFET cycles (44% vs. 22.5%; p = 0.044). For the entire cohort, ovulatory cycles and aFET were similar in terms of patient characteristics, demographics, infertility causes, treatment protocols and number of embryos transferred. Although the mean ESHRE score of the transferred embryos was higher in the aFET group, we found higher clinical pregnancy rate in the ovulatory cycle FET (41.3% vs. 27.3%, p < 0.0001). A better pregnancy rate was found after ovulatory cycle FET. In the ovulatory cycles, the outcome of letrozole-induced and non-induced cycles were comparable. PCOS patients, as well as the general population, may benefit from ovulation induced FET cycles, with significantly better outcomes in FET in ovulatory cycles.

More is not always better-lower estradiol to mature oocyte ratio improved IVF outcomes.

AIM: To find a cut-off ratio of estradiol/metaphase II oocyte (E2/M2) ratio and to evaluate the correlation with patients' characteristics, embryo morphokinetics using EmbryoScope™ and IVF cycle outcomes. MATERIAL AND METHODS: For this retrospective cohort study, records of all fresh cycles that were cultured and scored by EmbryoScope™ were evaluated. The peak E2/M2 ratio was calculated on the day of human chorionic gonadotropin (hCG) administration and correlated to embryo morphokinetic quality and cycle outcomes. A receiver operating characteristics analysis was calculated for the E2/M2 ratio and clinical pregnancy rates. RESULTS: A total of 2461 oocytes were collected from 319 patients. Receiver operating characteristics analysis revealed a cutoff of 204 as a discriminative point to predict clinical pregnancy with a sensitivity of 69.5% and specificity of 62.1% (P < 0.001). E2/M2 > 204 group were older, had higher E2 concentration, fewer M2 oocytes despite elevated gonadotrophin doses. E2/M2 ratio ≤ 204 was correlated with higher fertilization rate, better embryo quality, higher pregnancy and live birth rates, and more frozen embryos. CONCLUSION: E2/M2 ratio < 204 yielded the best probability to achieve good quality embryos with good morphokinetic scores and better pregnancy outcomes and may be used to predict IVF cycle outcomes. Advanced maternal age and low ovarian response received higher concentrations of gonadotrophins, which resulted in higher E2/M2 ratio. Milder stimulation to those patients may improve their cycle outcomes.

Comparable Outcomes Using Oral Dydrogesterone Vs. Micronized Vaginal Progesterone in Frozen Embryo Transfer: a Retrospective Cohort Study.

This retrospective study was conducted to determine whether using oral dydrogesterone (DYD) instead of micronized vaginal progesterone (MVP) in frozen embryo transfer (FET) cycles affects pregnancy outcomes. Women undergoing autologous FET in an academic fertility center were evaluated. Uses of 10 mg TID oral DYD or MVP for patients treated in FET cycles (artificial and ovulatory cycle, separately) were compared. The main outcome measure was live birth rates in each group. The study analyzed 599 cycles that occurred from January 2018 through December 2019. Chemical and clinical pregnancy rates were comparable between DYD vs. MVP groups (41.6% vs. 38.1%; P = 0.44 and 36.7% vs. 31.4%; P = 0.18, respectively). The ongoing pregnancy and delivery rates (29% vs. 22%, P = 0.06), as well as abortion rate (12.3% vs. 15.8%, P = 0.2), were comparable between the two groups. In a case-control sub-analysis of artificial FET cycles, we found comparable results between the two modes of luteal support. Similarly, results were comparable in ovulatory cycles using these medications for luteal support. Chemical and clinical pregnancy rates were comparable with DYD vs. MVP, in artificial FET (33.7% vs. 34.8%; P = 0.89 and 27.7% vs. 27.5%; P = 1), and in ovulatory FET (46.5% vs. 43.9%; P = 0.71 and 42.3% vs. 38.2%; P = 0.53), respectively. Our results indicate that in FET, pregnancy outcomes with oral DYD were not inferior to those with MVP.

The influence of obesity, smoking, and serum follicular stimulating hormone in azoospermic patients on testicular sperm extraction-intra cytoplasmic sperm injection outcomes: A retrospective cohort study.

To examine the effect of serum follicle-stimulating hormone (sFSH) level, body-mass index (BMI) and smoking on Testicular Sperm Extraction-Intracytoplasmic Sperm Injection (TESE-ICSI), and pregnancy outcomes.In this retrospective study, data were extracted from files of 52 azoospermic men who underwent TESE and in-vitro fertilization (IVF)-ICSI in our IVF unit. Demographic information, treatment cycle follow-up and pregnancy outcomes were collected.Fifty-two patients underwent 79 TESE due to azoospermia in 143 IVF cycles. Smoking was found to significantly affect sperm motility in TESE specimens before freezing (45.5% vs 14.8%; P <.001); however, this finding did not influence the pregnancy rate. Male FSH was inversely correlated with testicle volume (r = -0.595, P <.0001). Body weight did not affect semen parameters after TESE or ICSI outcomes.Among azoospermic patients with extremely poor sperm quality, male BMI, male FSH or smoking did not have an adverse effect sperm parameters or pregnancy and delivery rates.

Obesity results with smaller oocyte in in vitro fertilization/intracytoplasmic sperm injection cycles-a prospective study.

BACKGROUND: Obesity is associated with several fertility disorders. This prospective cohort study was designed to evaluate the effect of body mass index (BMI) (kg/m2) on oocyte diameter and treatment. METHODS: Women undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) were enrolled in the study. They were divided into two groups according to BMI: obese (BMI > 30) and normal weight (BMI < 25). Mature oocytes were evaluated according to total diameter, zona pellucida, and oolema diameters. RESULTS: A total of 387 oocytes were obtained from the 46 women who participated. Significantly more mature oocytes (M2) were retrieved from normal weight patients compare to obese women (15.1 ± 6.8 vs. 9.7 ± 3.9, respectively, P < 0.001). Oocytes from women in the obese group were significantly smaller than those in the normal weight group, including oocyte diameter (157.9 ± 7.9 vs. 164.3 ± 5.1 µm, P < 0.0001), oolema diameter (110.3 ± 4.5 vs. 113.5 ± 3.5 µm, P < 0.0001), and zona pellucida thickness (17.9 ± 2.6 vs. 19.0 ± 2.4 µm, P < 0.000), respectively. Multivariate logistic regression analysis, including oolema diameter, female age, BMI, number of M2 oocytes, and zona pellucida, was conducted to predict pregnancy. Small oolema diameter in obese patient adversely correlated with pregnancy. Larger oolema diameter was positively associated with the probability of pregnancy in the obese group as well as thinner zona pellucida. CONCLUSION: Obesity is associated with smaller oocytes, which adversely affect fertility outcomes. TRIAL REGISTRATION: NIH number NCT01672931.

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

Possible risk for cancer among children born following assisted reproductive technology in Israel.

BACKGROUND: Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant. METHODS: This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number. RESULTS: Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32). CONCLUSION: A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

Comparison between stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF with GnRH antagonist protocol.

PURPOSE: Highly purified Human Menopausal Gonadotropins (hp-hMG) and recombinant FSH (rFSH) are widely used in assisted reproductive technology (ART). The aim of this study was to compare ART results of the two preparations in GnRH antagonist cycles. METHODS: In this retrospective cohort study, IVF antagonist cycles performed from 2011 through 2013 were reviewed. There were 508 antagonist cycles: 320 stimulated with rFSH and 188 with hp-hMG. For every hp-hMG, two rFSH were matched for patient's age and infertility diagnosis. Subgroup analysis of patients younger and older than 35 was done as well. RESULTS: Both treatments were resulted in comparable pregnancy and live birth rates. However, cumulative pregnancy rates were higher for the rFSH group. In the matching analysis, the rFSH group had more mature oocytes and more embryos while using lower doses of gonadotropins. Pregnancy, cumulative pregnancy rates, and live birth rates were comparable. In the subgroup analysis, young patients in the rFSH group had better cycle outcomes compared with those in the hp-hMG group. CONCLUSION: In antagonist protocol, different gonadotropin products are equally effective. The choice of one or the other should depend on the availability, convenience of use, and cost.

Can intra cytoplasmatic morphologically selected sperm injection (IMSI) technique improve outcome in patients with repeated IVF-ICSI failure? a comparative study.

OBJECTIVE: Spermatozoal morphology was reported to effect fertilization, embryo quality and pregnancy results in spontaneous conception and ART. Intracytoplasmic morphologically selected sperm injection (IMSI) is an innovative, not invasive technique, which examines the sperm with no harm at a magnification of 6000 × in order to obtain optimal sperm to perform IVF-ICSI. We evaluated the efficiency of IMSI technique in patients with repeated IVF-ICSI failure of at least three cycles with no viable pregnancy and/or very poor sperm quality. STUDY DESIGN AND METHODS: All couples who performed IMSI between the years 2009 to 2012 were enrolled retrospectively to the study. Couples with male infertility who were treated with IMSI were included in the study. All their treatments were evaluated and divided into two subgroups: conventional IVF-ICSI treatment and their subsequent IMSI treatment. Demographic data, clinical parameters and outcome were recorded. The IMSI treatments were compared to previous non-IMSI treatments in terms of fertilization rates, cleavage rates, number of embryos and their quality, number of embryos transferred and pregnancy outcome. MAIN RESULTS: Forty-two couples were reviewed. Basic characteristics of the groups were comparable. Fertilization and cleavage rates of the two groups were comparable. The embryos quality demonstrated a trend toward superior quality (grade 1-2) embryos in the IMSI versus ICSI (60% versus 47%; p = 0.07 and 53% versus 40%; p = 0.07), respectively. Implantation and clinical pregnancy rates were significantly superior in IMSI group (19.2% versus 7.8%; p = 0.042 and 41.3% versus 10.5%; p = 0.02, respectively). Miscarriage rate was significantly higher in conventional IVF-ICSI group (100% versus 15.8%; p = 0.04), and live birth rate was significantly higher in IMSI group (0 in conventional IVF-ICSI and 34.7% per transfer in IMSI group; p = 0.003). CONCLUSION: IVF outcome of IMSI resulted in a higher implantation rate, pregnancy rate and most importantly delivery rate compare to non IMSI treated cycles.

Unusual case of recurrent heterotopic pregnancy after bilateral salpingectomy and literature review.

Heterotopic pregnancy occurs in up to 1% of pregnancies after IVF and embryo transfer. A case of a 35-year-old woman undergoing IVF treatment who had had previous laparoscopic bilateral salpingectomy due to hydrosalpinges is presented. She had had two heterotopic pregnancies in both tubal stumps in consecutive pregnancies achieved by IVF. The intrauterine pregnancies ended in spontaneous abortions. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in a cycle, especially when an inappropriately high serum ß-human chorionic gonadotrophin concentration is associated with an ultrasound finding of singleton intrauterine pregnancy.

Proangiogenic immature myeloid cells populate the human placenta and their presence correlates with placental and birthweight.

OBJECTIVE: To determine whether proangiogenic immature myeloid cells are present in human placentas. STUDY DESIGN: Biopsies were obtained from 61 placentas of term pregnancies. Percentage of CD45(+)CD33(+)LIN2(-)HLADR(-) immature myeloid cells of total CD45(+) hematopoietic cells was determined by flow cytometry. Location of immature myeloid cells in the placenta was identified using confocal microscopy. The proangiogenic potential of immature myeloid cells was analyzed by endothelial tube formation. RESULTS: Immature myeloid cells comprise ∼25% of human placental CD45(+) hematopoietic cells and infiltrate placentas in proximity of blood vessels. The percentage of immature myeloid cells correlated positively with placental weight (r(2) = 0.108, P = .01) and birthweight (r(2) = 0.087, P = .02). Endothelial tube formation was increased in the presence of immature myeloid cells as compared with the presence of CD45(+)LIN2(+) control cells. CONCLUSION: Human placentas are populated by immature myeloid cells in the proximity of blood vessels. Consistent with their involvement in angiogenesis, immature myeloid cells accelerated endothelial tube formation. The presence of immature myeloid cells in pathologic pregnancies warrants further studies.

CD11c+HLADR+ dendritic cells are present in human ovarian follicular fluid, and their maturity correlates with serum estradiol levels in response to gonadotropins.

OBJECTIVE: To determine whether dendritic cells (DCs), innate immune cells that specialize in initiation and modulation of immune responses, are present in ovarian follicular fluid (FF) and whether their abundance and maturation state correlate with ovarian response to gonadotropins. DESIGN: Observational study. SETTING: IVF unit and laboratory for reproductive immunology. PATIENT(S): Patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): FF was collected from the first follicle aspirated in each patient, and cellular content was analyzed by flow cytometry. DCs were defined as CD45(+)CD11c(+)HLADR(+)-cells, and the intensity of HLADR expression indicated DC maturity. RESULT(S): The CD45(+)-hematopoietic cell compartment in FFs (n = 30) contained a significant fraction of CD11c(+)HLADR(+) DCs (15.4% ± 2.9%). The mean fluorescence intensity (MFI) of HLADR expression, which reflects DC maturity, correlated positively with ovarian response to gondotropins, as determined by serum levels of E(2) on the day of hCG administration (r = 0.38). CONCLUSION(S): DCs make up a significant fraction of hematopoietic cells in the FF. Furthermore, DC maturation correlates positively with the ovarian response to gonadotropins. It is therefore conceivable that DCs contribute to the sterile inflammatory process in the follicle that leads to ovulation.

Maturation of human ovarian follicles is accompanied by a decrease in the CD56+CD16+ natural killer cell population.

OBJECTIVE: To investigate whether "proangiogenic" CD56+CD16- natural killer (NK) cells, which accumulate in follicular fluid (FF) of patients with a good response to ovarian stimulation, are also present in earlier stages of follicular development. DESIGN: Observational study. SETTING: Academic in vitro fertilization (IVF) unit. PATIENT(S): Patients of similar age and ovarian reserve, undergoing in vitro maturation (IVM; n=10) or IVF (n=22) cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): FF was collected from the first follicle aspirated in each ovary, and flow cytometry was used to define CD56+CD16- "proangiogenic" or CD56+CD16+ "cytotoxic" NK cells. RESULT(S): FF derived from antral follicles of patients undergoing IVM (maximum diameter 10 mm) showed a slightly higher abundance of "proangiogenic" NK cells compared with FF from preovulatory mature follicles (>18 mm) of patients undergoing IVF (5.4±1.3% vs. 3.0±1.1% of CD45+CD3- cells). Importantly, antral FF contained a significantly higher concentration of "cytotoxic" NK cells (11.4±2.3% vs. 3.7±0.9% of CD45+CD3- cells) compared with FF from mature follicles. CONCLUSION(S): "Proangiogenic" NK cells accumulate in ovarian follicles from as early as the antral follicular stage. Maturation of follicles is accompanied by a decrease in the population of "cytotoxic" NK cells that may have deleterious effects on follicular maturation.

[In vitro maturation of oocytes: a novel method of treatment of patients with polycystic ovarian syndrome undergoing in vitro fertilization].

BACKGROUND: In vitro maturation of oocytes (IVM) was developed to make in vitro fertilization (IVF) safer and simpler mainly for women with poLycystic ovarian syndrome (PCOS). The major benefits of IVM treatment include avoidance of hormone administration and risk of ovarian hyperstimulation syndrome (OHSS). OBJECTIVE: Results of IVM from our unit in patients with PCOS. METHODS: In this study 85 PCOS patients underwent 102 IVF cycles of IVM and were treated with one of the following protocols: (1) Priming with 150 units of recombinant FSH for 3 days, from the 3rd day of menses, following follicle development up to 10-12 mm. (2) Administration of 17beta estradiol (estrofem) on second day of menses, followed by ultrasound endometrial measurement up to > or =6 mm. thickness. Oocytes were collected 38 hours post recombinant human chorionic gonadotropin (rhCG) administration. Luteal phase support was achieved by estrofem and progesterone. Oocytes were matured either 6-30 hours (protocol 1) or 24-48 hours (protocol 2) in IVM medium and fertilized by intracytoplasmatic sperm injection (ICSI). Mean number of immature oocytes collected, maturation, fertilization, cleavage and pregnancy rates were assessed. RESULTS: Total number of retrieved oocytes was 1224 (mean 12 +/- 6.2 per cycle); 820 (64.9%) underwent maturation after 6-48 hours of culture while 128 of them (15.6%) after 6 hours and 20.2% of transferred embryos originated from those oocytes. FertiLization rate was 47.2%. Pregnancy and implantation rates were 28.4% and 11.25% respectively. CONCLUSIONS: IVM appears to be a simpler and tolerable treatment method in patients with PCOS undergoing IVF treatment. Favorable results were obtained.

A prospective randomized controlled trial of Wallace and Rocket embryo transfer catheters.

The aim of this study was to compare the efficacy of two embryo transfer catheters: Wallace and Rocket Embryon in an IVF programme of a tertiary referral university centre. A total of 308 patients undergoing embryo transfer were prospectively randomized to either a transfer with the Wallace catheter or a transfer with the Rocket catheter. The main outcome measure in this study was the clinical pregnancy rate, and secondary outcome measures included implantation rate, visibility of the catheter under ultrasound, number of retained embryos post transfer, and whether change of catheter was required. In addition, patient discomfort during the procedure was recorded. Pregnancy and implantation rates were similar when Wallace or Rocket catheters were used. However, for the Rocket catheter, the tip was more often clearly seen on ultrasound and it had a lower rate of retained embryos in the catheter after transfer (P < 0.05). Experience with different transfer catheters is recommended for difficult cases.

Does the presence of nuclear vacuoles in human sperm selected for ICSI affect pregnancy outcome?

BACKGROUND: To verify whether or not microinjection of sperm with a normal nuclear shape but large vacuoles affects IVF-ICSI pregnancy outcome. METHODS: A comparative study testing IVF outcome parameters of IVF-ICSI, based on morphological selection of spermatozoa with normal nuclei against those based on microinjection of sperm with a normal nuclear shape but large vacuoles. An experimental group, including 28 IVF-ICSI cycles, where only embryos obtained from microinjection of spermatozoa with a normal nuclear shape but large vacuoles were transferred, was matched with a control group, including 28 IVF-ICSI cycles, where only embryos obtained from microinjection of spermatozoa with a strictly defined morphologically normal nuclear shape and content were transferred. The main outcome was IVF-ICSI pregnancy rate. RESULTS: The experimental group exhibited a significantly lower pregnancy rate per cycle and significantly higher abortion rate per pregnancy compared to the control group (18 versus 50%, and 80 versus 7%, respectively, P=0.01). CONCLUSION: Microinjection of vacuolated sperm appears to reduce the pregnancy rate and appears to be associated with early abortion.