Pregnancy potential and perinatal outcomes of embryos cryopreserved twice: a case-control study.

RESEARCH QUESTION: What are the pregnancy and perinatal outcomes of twice-cryopreserved embryos compared with embryos cryopreserved once? DESIGN: Retrospective register-based case-control study. The case group consisted of transfers of twice-cryopreserved embryos (n = 89), and the control group of transfers of embryos cryopreserved once (n = 304). Matching criteria were embryonic age at transfer and female age category of less than 35 years or 35 and greater. RESULTS: The survival rate of twice-cryopreserved embryos was 92.2%, and 93.7% of the planned frozen embryo transfers (FET) could be completed. FET was performed with cleavage-stage embryos in 17 cases and 68 controls and with blastocysts in 72 cases and 238 controls. The rates of live birth (27.0% versus 31.9%, adjusted odds ratio [OR] 0.70, 95% CI 0.40-1.22, P = 0.21), clinical pregnancy (31.5% versus 36.8%, adjusted OR 0.71, 95% CI 0.42-1.21, P = 0.21) and miscarriage (4.5% versus 3.9%, adjusted OR 1.10, 95% CI 0.33-3.60, P = 0.88) in the case and the control groups were comparable. No difference was seen in the preterm delivery rate (cases 4.2% versus controls 10.3%, P = 0.69). Twenty-five children were born in the case group and 100 in the control group. No difference in birthweight was detected between the groups and there were no large for gestational age fetuses or congenital malformations in the case group. CONCLUSIONS: Uncompromised live birth rates and neonatal outcomes may be expected after the transfer of twice-cryopreserved embryos. To avoid embryo wastage and transfer of multiple embryos, good quality surplus embryos from FET cycles may be cryopreserved again by vitrification.

Multinucleation in Day Two Embryos Is Not Associated with Multinucleation in Sibling Embryos After Freezing and Thawing.

BACKGROUND: Multinucleated embryos exhibit impaired implantation potential, but whether the presence of multinucleated embryos in an embryo cohort reflects the quality of the entire cohort is controversial. No data exists on multinucleation rate among frozen-thawed embryos. METHODS: De novo multinucleation and the number of multinucleated embryos on day two of embryo culture before freezing (D2) (n=415), at thawing (D2t) (n=320) and after an overnight culture after thawing (D3t) (n=265) was recorded. Associations between multinucleation before and after cryopreservation, female age and ovarian sensitivity to hormonal stimulation were assessed. RESULTS: The occurrence of at least one multinucleated embryo per embryo cohort was 62.4% on D2, 16.3% on D2t and 31.7% on D3t. The presence of multinucleated embryos prior to freezing was not associated with de novo multinucleation during post-thaw culture (p=0.845). On D2, multinucleation was high in young women, irrespective of the number of collected oocytes (p=0.702). In older age groups, multinucleation was highest if >17 oocytes were obtained (p<0.001) and the odds for multinucleation was the lowest if the consumption of recombinant follicle-stimulating hormone was >238 IU/oocyte (In the age group of 30-35 years OR 0.25 [0.13-0.47], and the age group of 36-40 years OR 0.35 [0.20-0.63]. CONCLUSION: Multinucleation is commonly seen in embryos and good-quality day two embryo cohorts before freezing. The presence of multinucleated embryos prior to freezing does not illustrate multinucleation in sibling embryos after thawing. Embryo multinucleation is associated with factors related to good prognosis in assisted reproduction treatments.

Mid-luteal phase gonadotropin-releasing hormone agonist support in frozen-thawed embryo transfers during artificial cycles: A prospective interventional pilot study.

OBJECTIVE: To assess the effect of an additional single mid-luteal dose of gonadotropin-releasing hormone agonist (GnRHa) on pregnancy and perinatal outcomes in hormonally substituted frozen embryo transfer (FET) cycles. STUDY DESIGN: A prospective interventional pilot study. Women scheduled for FET were randomly selected to receive standard hormonal replacement therapy (HRT) for endometrial preparation or HRT with a single additional subcutaneous dose of 0.1mg triptorelin at the time of implantation. If FET was not followed by a pregnancy, women with surplus embryos were scheduled for a single second attempt in a crossover setting. Altogether, 144 FET cycles were analyzed. The carryover effect was tested using a logistic regression model. Logistic regression analysis for binary variables was applied with generalized estimation equation extension to account for dependence among repeated treatments. RESULTS: The live birth rate (LBR) was 9.8 percentage points higher and the miscarriage rate 14.7 percentage points lower in the intervention group (n=72) than in the control group (n=72), but the differences did not reach statistical significance. Implantation and clinical pregnancy rates were comparable between the groups. No congenital malformations or differences in the median birth weight of newborns were detected. CONCLUSIONS: Observable but statistically insignificant difference in LBR and miscarriage rate favoring luteal phase GnRHa support was detected. Further, no malformations or effect on fetal growth were observed. Larger studies are needed to confirm the results of this pilot study.

Pregnancy and perinatal outcomes after transfer of binucleated or multinucleated frozen-thawed embryos: a case-control study.

Blastomere multinucleation in human embryos is a common phenomenon, but data on its effect on pregnancy outcome and the health of newborns are scarce. In this case-control study, we assessed pregnancy and perinatal outcomes from 136 binucleated and multinucleated frozen-thawed embryo transfer cycles against a control group of 136 non-binucleated and multinucleated frozen embryo transfer cycles. Clinical pregnancy and live birth rates were lower among the case group (29.4% versus 44.1%, P = 0.012; 22.1% versus 36.0%, P = 0.011, respectively), but perinatal outcomes (gestational week at delivery, birth weight, placental weight and occurrence of congenital anomalies) were similar. Live birth rates among patients receiving embryos with multinucleation compared with binucleation was not significantly different (24.7% versus 13.2%). Consequently, frozen-thawed cleavage-stage embryos with bi- or multinucleation have lower than normal but still acceptable implantation potential and ability to produce healthy pregnancies and newborns. The study is limited by its retrospective nature. Time-lapse monitoring would be a more sensitive method of detecting multinucleation. Controls and cases were matched only by age at the time of oocyte retrieval, and other characteristics were only interpreted statistically. Although larger than previously reported, the number of cases is limited.

The management of polyps in female reproductive organs.

Polyps of the lower reproductive tract are found in 7.8-50% of women. It has been hypothesized that cytogenetic modifications on chromosomes 6, 7 and 12 as well as epigenetic factors involving enzyme and metabolic activities may cause polyps to develop. Cervical polyps found in 2-5% of cases are of low clinical significance and can cause, although rarely, post coital bleedings. Cervical polyps grow during pregnancy and mucorrhoea. Trans vaginal ultrasound (TVU) provides an excellent diagnostic technique to diagnose the size and the anatomic location of endometrial polyps (EPs). In asymptomatic young woman with small EPs <10 mm in size, conservative management can be safely followed by monitoring the polyp growth. EPs located at the fundal and tubocornual regions mechanically affect fertility and disturb normal cellular function due to chronic inflammation. In cases where Eps are a cause of subfertility mechanical hysteroscopic resection is advisable. When the sole reason for infertility is an EP, the patient often becomes spontaneously pregnant shortly after removal. EP Detection in either peri- or post-menopausal age, in symptomatic or asymptomatic patients calls for meticulous hysteroscopic examination and polypectomy is mandatory. Endometrial curettage is also recommended to rule out sub clinical endometrial hyperplasia or cancer. Hysteroscopic surgery for large EPs using bipolar resectoscopes, hysteroscopic morcellators or shavers are considered equally efficient and safe under general anaesthesia. Recurrence rate of EPs after resection is unknown. The recent advances in TVU and hysteroscopy, however, should provide an accurate diagnosis and effective treatment of polyp in the female reproductive tract with minimal recurrence or surgery complications. The significantly increased incidence of colorectal polyps in cohorts that also had EPs might indicate that patients with EPs should be also referred for colonoscopy. EPs have the lowest incidence of malignant transformation as compared to colon, urinary bladder, oropharyngeal, nasal and laryngeal carcinomas.

[Adenomyosis - diagnostic and therapeutic challenge]. / Kohdun adenomyoosi - diagnostinen ja hoidollinen haste.

In adenomyosis, endometrial glandular and stromal cells grow inside the myometrium, and form localized or diffusely expanding islets. Smooth muscle cells of the uterus surrounding the adenomyosis colonies become hypertrophic, which may lead to abnormal contractions of the uterine wall. Adenomyosis is an estrogen-dependent disease with abnormal uterine bleeding and dysmenorrhea as typical symptoms. The disease may even be asymptomate. The diagnosis is made by histologically or ultrasonic or MRI imaging. Adenomyosis can be treated with hormonal medications. Fertility-sparing radiologic and surgical techniques are also available.

Effect of mid-luteal phase GnRH agonist on frozen-thawed embryo transfers during natural menstrual cycles: a randomised clinical pilot study.

This prospective randomised crossover study evaluated the effect of mid-luteal single-dose gonadotropin-releasing hormone agonist (triptoreline) on pregnancy outcomes in natural-cycle frozen embryo transfers (FETs). Ninety-eight women were randomised to receive either standard luteal support with vaginal micronised progesterone or an additional single dose of 0.1 mg triptoreline at the time of implantation. The intervention group was composed of 65 FET cycles and the control group of 62 cycles. In the intervention group, there were more positive pregnancy tests, clinical pregnancies and live births, but the differences did not reach statistical significance. The mean beta human chorionic gonadotropin (ß-hCG) concentration of singleton pregnancies was significantly lower in the intervention group compared to the control group (p = 0.048). No difference was detected in the median birth weight of the newborns.

A case of conjoined twins after a transfer of a multinuclear embryo.

A pregnancy with conjoined twins was observed after transfer of a multinuclear embryo. As nuclear mechanisms have a role in cellular differentiation, association between multinucleation and fetal malformations is possible. Follow-up studies on children born after transfer of embryos with bi/multinuclear blastomeres are needed.