The freezing method of cleavage stage embryos has no impact on the weight of the newborns.

PURPOSE: The aim of this study was to study the effect of the embryo freezing method on the birth weight of newborns from frozen embryo transfer (FET) cycles, and the pregnancy results of cleavage stage embryos cryopreserved by slow freezing or vitrification. METHODS: This is a retrospective cohort study undertaken in a University Hospital IVF unit using concurrently both the slow-freezing and the vitrification techniques. All frozen-thawed and vitrified-warmed day 2 and day 3 embryo transfers during the time period from 1 April 2009 to 31 November 2013 were included in the study. RESULTS: There was no statistically significant weight difference between newborns from vitrified or slow-frozen embryos (3588 vs 3670 g). A higher post-thaw viability rate was achieved after cryopreservation by the vitrification technique compared to the slow-freezing protocol (83.4 vs 61.4%). The miscarriage rate was lower in the vitrification group (15.7 vs 29.0%). The live birth rates were similar (19.5 vs 19.1%) in the slow-freezing and vitrification groups, respectively. Among vitrified embryos, 7.4 embryos needed to be thawed to produce one delivery; in the slow-freezing group, that number was 11.9. CONCLUSIONS: The freezing method has no impact on the weight of the newborn. With lower post-thaw survival rates and higher miscarriage rates, the slow-freezing cryopreservation protocol is inferior to the vitrification technique.

Male gender explains increased birthweight in children born after transfer of blastocysts.

STUDY QUESTION: Does extended embryo culture have a different effect on the birthweight of girls and boys? SUMMARY ANSWER: The mean birthweight of boys born after fresh and frozen-thawed blastocyst transfer was increased compared with those born after cleavage stage embryo transfer. This effect was not detected among girls. WHAT IS KNOWN ALREADY: Previous studies indicate that newborns from frozen-thawed cleavage stage embryos may present with a higher weight than newborns from fresh embryo transfers. With regard to fresh embryos, newborns after a blastocyst transfer have been reported as having higher birthweights than newborns from cleavage stage embryos. STUDY DESIGN, SIZE, DURATION: Retrospective multicentre case-control cohort study. All IVF/ICSI treatments were performed in the time-period from January 2008 to March 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Birthweight of singletons born at full-term (≥37 weeks), after fresh or frozen blastocyst embryo transfers (n = 277), were compared with weights of children born after fresh or frozen cleavage stage embryo transfers (Day 2-3) (n = 277). The cases and controls were matched by delivery week, and by gender. Data of IVF/ICSI treatments, and the treatments' outcomes were collected and analysed. MAIN RESULTS AND THE ROLE OF CHANCE: The birthweight after a fresh blastocyst transfer was significantly higher (mean 3530.6 g) than that after a transfer of cleavage stage embryos (mean 3418.8 g; weight difference 111.8 g, P = 0.047). The weights of newborns after frozen-thawed blastocyst transfers (mean 3647.5 g) and the frozen-thawed cleavage stage embryo transfers (mean 3650.9 g), were similar (weight difference 3.4 g, P = 0.95). The boys born after transfer of frozen-thawed blastocysts had a significantly higher birthweight (mean 3767.9 g) than girls (3525.2 g; weight difference 242.7 g, P = 0.002), whereas the difference of birthweights between genders was only 13.5 g in cleavage stage (P = 0.863). The same effect was seen after fresh blastocyst transfers (weight difference 211.5 g, P = 0.011), but not after fresh Day 2-3 embryo transfers (weight difference 53.6 g, P = 0.478). LIMITATIONS, REASONS FOR CAUTION: The study material was large enough to detect differences between birthweights as a whole, but a larger study group would confirm these new findings. To avoid selection bias, the next possible control candidate, fulfilling the selection criteria, was included for matching cases and controls. We have matched the cases and controls by gender and gestational week at birth, with an aim to reduce their impact as confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Our findings of a similar weight at birth of newborns after frozen-thawed blastocysts and frozen-thawed cleavage stage embryos, when matching for age and duration of pregnancy, are novel. The gender of the newborn has an impact on the birthweight, and the extended embryo culture increases the weight difference between the genders, which is a new finding as well. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Fertility Society of Finland.

Low-dose aspirin does not improve ovarian responsiveness or pregnancy rate in IVF and ICSI patients: a randomized, placebo-controlled double-blind study.

BACKGROUND: Poor ovarian and endometrial responses to gonadotrophin stimulation in assisted reproduction techniques lead to decreased pregnancy rates. The aim of the present study was to test the hypothesis that low-dose aspirin started prior to controlled ovarian stimulation improves ovarian responsiveness, pregnancy rate (PR) and pregnancy outcome. METHODS: A total of 374 women who were to undergo IVF/ICSI were randomized to receive 100 mg of aspirin (n=186) or placebo (n=188) daily. Treatment was started on the first day of controlled ovarian stimulation. It was continued until menstruation or a negative pregnancy test. Pregnant women continued the medication until delivery. The main outcome measures were the number of oocytes, number and quality of embryos, the clinical PR and pregnancy outcome. RESULTS: The mean (+/-SD) number of oocytes (12.0+/-7.0 versus 12.7+/-7.2), the total mean number of embryos (5.82+/-4.35 versus 5.99+/-4.66), the mean number of top quality embryos (0.99+/-1.39 versus 1.18+/-1.51) and the number of embryos transferred (1.64+/-0.64 versus 1.63+/-0.71) did not differ in the aspirin and placebo groups. Between the aspirin and placebo group, there was no statistically significant difference in clinical PR per embryo transfer (25.3%, n=44 out of 174 versus 27.4%, n=48 out of 175) or clinical PR per cycle initiated (23.7% versus 25.5%). Birth rate per embryo transfer did not differ significantly between the aspirin (18.4%) and placebo (21.1%) groups. The incidence of poor responders [12 (6.5%) versus 13 (6.9%)] was similar in both groups. CONCLUSIONS: The present results indicate that low-dose aspirin treatment does not have any beneficial effect on ovarian responsiveness, PR and pregnancy outcome in unselected women undergoing IVF/ICSI.

Correlation between serum inhibin B and other indicators of the ovarian function.

OBJECTIVE: To investigate the correlation between the early follicular phase serum inhibin B levels and other indicators of ovarian reserve. STUDY DESIGN: Seventy-four women aged 24-40 years (mean 32) with different infertility etiologies were investigated in the early follicular phase of a spontaneous mentrual cycle. The volume of the ovaries was measured and the total number of follicles <5 mm in size counted by ultrasound. Serum levels of FSH, estradiol (E2) and inhibin B were measured on the same day. In stepwise regression analysis inhibin B levels were correlated with age, body-mass-index, the ultrasound measurements, cause of infertility, parity, FSH and E2. RESULTS: FSH, BMI and the number of follicles proved to be statistically significant independent predictive factors for the inhibin B levels, FSH and BMI correlating negatively and the number of follicles positively with inhibin B serum concentrations. CONCLUSION: The number of small follicles reflect the inhibin B production of the ovaries. BMI being as strong predictive factor of inhibin B levels as FSH could in part explain the impaired likelihood of conceiving in obese patients.

In vitro fertilization in patients with ovarian endometriomas.

OBJECTIVE: The objective of the study was to establish whether operative treatment of recurrent ovarian endometriosis improves the prognosis of in vitro fertilization. METHODS AND MATERIAL: A retrospective analysis of one hundred endometriosis patients admitted to Tampere University Hospital for IVF treatment. Forty-five patients had an ovarian endometrioma during IVF treatment, 36 of the cases being recurrences after a previous operation. Fifty-five patients had ovarian endometriomas operated without recurrence. The patient groups with or without endometriosis did not differ in age, duration of infertility, sperm parameters, amount of gonadotropins required per oocyte and number of retrieved oocytes. RESULTS: The patients with ovarian endometriosis had more embryos (mean 3.9) than women without endometriomas (mean 2.8) (p<0.05) and the respective pregnancy rates per IVF cycle were 38% and 22%. Patients with endometriomas had a live birth rate of 27% compared with 20% in women with no endometriomas. CONCLUSIONS: The presence of a small endometrioma does not reduce the success of IVF treatment.

Prognostic factors in controlled ovarian hyperstimulation.

OBJECTIVE: To determine whether the number of retrieved oocytes and the required amount of gonadotropins per oocyte in IVF treatment can be predicted with use of the following independent predictive variables: age, parity, cause of infertility, body mass index, day 3-5 FSH, E2, inhibin B, ovarian volume, the number of follicles, and intraovarian and uterine artery vascular resistance measured by ultrasonography before ovarian hyperstimulation. DESIGN: A retrospective analysis. SETTING: University hospital infertility clinic. PATIENT(S): Seventy-four consecutive women attending the university hospital infertility clinic for IVF treatment. INTERVENTION(S): The investigated factors were measured on day 3-5 of the cycle, in which luteal phase suppression was begun before ovarian hyperstimulation preparatory to IVF. MAIN OUTCOME MEASURE(S): The amount of gonadotropins required per oocyte and the number of retrieved oocytes were correlated with the predictive factors in stepwise regression analysis. RESULT(S): The best predictive factors for the number of oocytes retrieved were FSH, inhibin B, and parity, explaining 25% of the ovarian response. Intraovarian vascular resistance, parity, FSH, and inhibin B best predicted the amount of gonadotropins needed, explaining 44% of the variation. CONCLUSION(S): FSH, inhibin B, and parity were the independent predictive factors for the number of retrieved oocytes. The same factors and intraovarian vascular resistance predicted the required amount of gonadotropins per oocyte. The main part of the ovarian response cannot be predicted using the factors investigated.

The association between hormone levels and vascular resistance in uterine and ovarian arteries in spontaneous menstrual cycles--a Doppler ultrasound study.

Ninety-four infertility patients were studied by Doppler ultrasound during spontaneous ovulatory menstrual cycles. The pulsatility index (PI) in uterine and ovarian arteries was measured in the follicular and midluteal phase of the cycle. Associations between high PI values and hormones (estradiol, progesterone, prolactin, testosterone, follicle stimulating hormone) measured during the investigated cycle and age were evaluated. A high PI in uterine arteries in the follicular phase was associated with low estradiol (E2) and progesterone (P) levels in the studied cycle. In the luteal phase PI values of uterine arteries have no obvious association with E and P levels, and other vasoactive compounds influence the perfusion of uterus during this period. The other hormones analysed and age did not correlate with vascular resistance in spontaneous ovulatory cycles.

The reproducibility of the Doppler ultrasound measurement of uterine artery vascular resistance.

The intra- and interobserver variation in Doppler ultrasound measurements of uterine arteries (UA) and the variation of pulsatility index (PI) in UA in successive menstrual cycles in the same patient was studied. The intra- and interobserver variability of measurements was similar. In all three series the difference between two measurements was smaller with lower PI values. Cycle-dependent changes, biological variation and random measurement are foremost in causing variability and no systematic error was evident. Doppler ultrasound measurements from UA can be used when patient groups are compared, but in the case of an individual patient, large limits of agreement must be borne in mind.

Vascular resistance in uterine and ovarian arteries: its association with infertility and the prognosis of infertility.

In this study we investigated the blood flow in uterine (u.a.) and ovarian arteries (o.a.) in healthy women and infertility patients and the relationship of vascular resistance to the etiology and the prognosis of infertility. A total of 101 consecutive infertility patients referred to hospital for investigations were studied by Doppler ultrasound. Couples with male infertility were excluded. The control group comprised 19 healthy women having regular menstrual cycle and no history of infertility. The pulsatility index (PI) in o.a. and u.a. was measured in pre- and post-ovulatory phase of the menstrual cycle. The PI values of the controls were compared with those of the patients with various infertility etiologies. The PI values of the infertility patients who subsequently delivered were compared with those of the patients failing to deliver. Infertility patients had high PI in o.a. and u.a. in the luteal phase more often than controls. High vascular resistance in u.a. and o.a. in the luteal phase reduce the take-baby-home rate.

The role of vascularisation of the corpus luteum in the short luteal phase studied by Doppler ultrasound.

One hundred infertility patients were investigated by Doppler ultrasound and 17 were found to have a short luteal phase (< 10 days) (SLP), which is regarded a subgroup of luteal insufficiency (LPD). The vascularisation within the corpus luteum (CL) was investigated using vaginal Doppler ultrasound. The values were compared with those of a control material. In both groups the resistance to blood flow was lowest on the fifth postovulatory day and grew from the ninth postovulatory day towards the end of the luteal phase. The results in these groups did not differ significantly. In both groups serum progesterone values had a slight negative correlation with pulsatility index (PI) and resistance index (RI) measured within the CL. The defect in vascularisation of the CL is not a reason for SLP, and Doppler ultrasound measurements from the CL do not help in the diagnosis of SLP.

Doppler ultrasound findings in tubo-ovarian infectious complex.

Ten women with tubo-ovarian infectious complex caused by pelvic inflammatory disease were investigated with vaginal Doppler sonography during the acute and healing phase of the infection. Doppler velocity waveforms were quantitated by the resistance index (RI) and pulsatility index (PI). A low resistance blood flow was found at the margin of the infectious complex. An RI' value < 0.5 was detected in 6 patients in the acute or subacute phase of infection. The severity of the infection as determined by C-reactive protein values was inversely correlated to RI and PI. The process of angioneogenesis is speculated to be responsible for this increased flow. The tubo-ovarian infectious process must be remembered in the differential diagnosis, when an adnexal mass with low resistance blood flow is found in the ultrasound examination.

Catecholamine concentrations in venous plasma and cerebrospinal fluid in normal and complicated pregnancy.

The concentrations of adrenaline and noradrenaline were determined in venous plasma and cerebrospinal fluid (CSF) of 41 pregnant women at term scheduled for elective or 'hot' caesarean section and in 7 healthy non-pregnant women scheduled for elective surgery. Group 1: 10 pregnant women at term with a normal history of their pregnancy; group 2: like group 1, but in active labour for more than 4 h; group 3: 10 pregnant women with insulin-dependent diabetes mellitus with or without slightly elevated arterial blood pressure; group 4: 11 women with pre-eclampsia gravis; group 5: 7 healthy non-pregnant women of fertile age. The highest values of mean arterial blood pressure and of venous plasma noradrenaline were found in the pre-eclamptic group 4, mean arterial blood pressure and plasma noradrenaline levels correlated to each other. However, concentrations of noradrenaline in CSF in group 4 did not differ significantly from the other groups. It is speculated that a different origin of hypertension may be the reason for the normal noradrenaline concentrations in CSF. This finding is in contrast to earlier findings in which noradrenaline levels in CSF were elevated in patients with essential hypertension.

Doppler ultrasound studies in pelvic inflammatory disease.

Ten women with tubo-ovarian abscess caused by pelvic inflammatory disease (PID) were investigated by transvaginal Doppler ultrasound during the acute and healing phases of the infection. The pulsatility index (PI) of the uterine arteries was measured and compared with the values obtained from 19 healthy women. Each control patient was investigated three times during a single menstrual cycle. In PID patients, the PI values were significantly lower than in controls in the same phase of the menstrual cycle. When C-reactive protein was > 50, the PI values were lowest and reverted to normal values when the infection subsided. In a case of chronic infection, the PI did not rise to normal despite normal infection parameters. Doppler ultrasound seems to offer a new method of assessing PID.