In vitro maturation (IVM) of oocytes is a laboratory method that allows the maturation of immature (GV) oocytes retrieved from patients enrolled in the in vitro fertilization (IVF) programme. ...However, this method is still sparsely researched and used in clinical practice, leading to suboptimal clinical results. Anti-Müllerian hormone (AMH) is an important hormone with known effects on human ovaries, especially on follicles (follicular cells) during folliculogenesis. In contrast, the effect of AMH on the human oocyte itself is unknown. Therefore, we wanted to determine whether human oocytes express AMH receptor 2 (AMHR2) for this hormone. Recombinant AMH was added to the IVM medium to determine whether it affected oocyte maturation.
In total, 247 human oocytes (171 immature and 76 mature) were collected from patients enrolled in the intracytoplasmic sperm injection (ICSI) programme who were aged 20 to 43 years and underwent a short antagonist protocol of ovarian stimulation. The expression of AMHR2 protein and AMHR2 gene was analysed in immature and mature oocytes. Additionally, maturation of GV oocytes was performed in vitro in different maturation media with or without added AMH to evaluate the effect of AMH on the oocyte maturation rate.
Immunocytochemistry and confocal microscopy revealed that AMHR2 protein is expressed in both immature and mature human oocytes. AMHR2 was expressed in a spotted pattern throughout the whole oocyte. The IVM procedure revealed that AMH in maturation medium improved GV oocyte maturation in vitro, as all oocytes were successfully matured in maturation medium containing recombinant AMH only. Furthermore, antagonism between AMH and follicle-stimulating hormone (FSH) during the maturation process was observed, with fewer oocytes maturing when both AMH and FSH were added to the maturation medium. Finally, AMHR2 gene expression was found in immature and in vitro matured oocytes but absent in mature oocytes.
The positive AMHR2 protein and AMHR2 gene expression in human oocytes shows that AMH could directly act on human oocytes. This was further functionally confirmed by the IVM procedure. These findings suggest the potential clinical application of recombinant AMH to improve IVM of human oocytes in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of our study was to explore the risk factors for very preterm (gestation under 32 weeks) and moderate preterm birth (gestation weeks 32-36 6/7) in singleton pregnancies in a national ...retrospective cohort study. We also wanted to establish whether IVF/ICSI is an independent risk factor for preterm birth after adjusting for already known confounders. We used data for 267 718 singleton births from 2002-2015 from the National Perinatal Information System of Slovenia, containing data on woman, pregnancy, birth, the postpartum period, and the neonate for each mother–infant pair. Mode of conception, maternal age, education, BMI, parity, smoking, history of cervical excision procedure, history of hysteroscopic resection of uterine septum, presence of other congenital uterine malformations, bleeding in pregnancy, preeclampsia or HELLP and maternal heart, and pulmonary or renal illness were included in the analyses. Unadjusted OR for very preterm birth after IVF-ICSI was 2.8 and for moderate preterm birth was 1.7. After adjusting for known confounders, the OR was still significantly elevated (1.6 and 1.3, respectively). Risk factors for very preterm birth with OR higher than 2.4 were history of cervical excision procedure, resection of uterine septum, operation or having other congenital uterine malformations, and bleeding in pregnancy. Risk factors for very preterm birth with OR between 1.4 and 2.1 were age >35 years, being underweight or obese, not having professional education, smoking, first birth, preeclampsia/HELLP, and IVF/ICSI. Risk factors for moderate preterm birth with OR higher than 2.4 were history of cold knife conization and other congenital uterine malformations. We found that even after adjustment, IVF/ICSI represents a single risk factor for early and late preterm birth even after adjustment with other risks such as maternal age, smoking, or a history of invasive procedures for either cervical intraepithelial neoplasia or infertility treatment.
This study compared serum and follicular anti-müllerian hormone, LH, FSH, E2 , and P concentrations in modified natural cycles and controlled ovarian hyperstimulation cycles to analyze their effect ...on oocyte and embryo quality and implantation. Follicular anti-müllerian hormone, FSH, E2 , and P concentrations had no effect on embryo quality, whereas high serum and follicular LH concentrations in natural cycles modified only with hCG did not compromise oocyte and embryo quality but might have a negative effect on implantation.
Purpose
The present study aimed to determine clinical IVF parameters and gene expression in cumulus cells (CCs) in obese and normal weighting women after administration of 150 mcg of corifollitropin ...alfa for controlled ovarian hyperstimulation (COH).
Methods
150 mcg of corifollitropin alfa and gonadotropin releasing hormone antagonist were used for COH. Analysis of CC gene expression was performed using quantitative real-time PCR.
Results
We did not find significant differences in biochemical and clinical pregnancy rates between obese and normal weighting women. Obese women required twice as much of additional gonadotropins for ovarian stimulation and had a significantly lower proportion of good quality embryos on day 5 of IVF cycle. Expression of
PGR
and
PTX3
was significantly higher in CCs of obese women.
Conclusion
Obese women require significantly larger amounts of gonadotropins to achieve similar IVF success rates as normal weighting women. Differences in CC gene expression and smaller proportion of good quality embryos may imply that oocytes derived from obese women are of lower quality. Further studies are needed to evaluate whether obesity itself or the higher amount of gonadotropins used in obese women causes this effect.
In an in vitro fertilization program, approximately 10-15% of oocytes obtained after controlled ovarian stimulation are immature, with germinal vesicles (GVs). These oocytes are usually discarded in ...clinical practice; however, an in vitro maturation (IVM) procedure can be applied to mature them. There are scarce data in the literature on the effect of IVM on the expression of important development- and zona pellucida (ZP)-related genes in human oocytes; therefore, we wanted to determine this. One hundred nine human oocytes were collected from patients enrolled in an intracytoplasmic sperm injection program. The expression of the BMP4, GDF9, ZP1, ZP2, ZP3, and ZP4 genes was analyzed using RT-qPCR in oocytes matured in vitro with different reproductive hormones in the IVM medium (AMH, FSH + hCG, FSH + hCG + AMH), in in vivo matured oocytes and in immature oocytes with GVs. No statistically significant differences in the expression of selected genes in oocytes were observed among groups with different reproductive hormones in IVM medium. However, several interesting significant correlations were found between BMP4 and GDF9, and ZP1 and ZP4; between GDF9 and ZP1, and ZP2 and ZP4; and between ZP1 and ZP3 and ZP4 in the in vitro matured oocytes, while no such correlations were present in other groups of oocytes. The type of reproductive hormone in the maturation medium does not affect the expression of the analyzed genes in oocytes during the maturation process. However, the in vitro maturation procedure itself generated correlations among analyzed genes that were otherwise not present in in vivo matured and immature oocytes.
Abstract Objectives Our aim was to explore the association between cold-knife conisation and large loop excision of transformation zone (LLETZ) with spontaneous preterm birth in a large 10-year ...national sample. We wanted to explore further the association of these procedures with preterm birth according to gestation. Study Design We conducted a population based retrospective cohort study, using data from national Medical Birth Registry. The study population consisted of all women giving birth to singletons in the period 2003–2012 in Slovenia, excluding all induced labours and elective cesarean sections before 37 weeks of gestation (N = 192 730). We compared the prevalence of spontaneous preterm births (before 28 weeks, before 32 weeks, before 34 weeks and before 37 weeks of gestation) in women with cold-knife conisation or LLETZ compared to women without history of conisation, calculating odds ratios (OR), adjusted for potential confounders. Chi-square test was used for descriptive analysis. Logistic regression analyses were performed to estimate crude odds ratio (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) with two-sided probability ( p ) values. Results A total of 8420 (4.4%) women had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks of gestation and 603 (0.3%) before 28 weeks of gestation. A total of 4580 (2.4%) women had some type of conisation in their medical history: 2083 (1.1%) had cold-knife conisation and 2498 (1.3%) had LLETZ. In women with history of cold-knife conisation, the adjusted OR for preterm birth before 37 weeks of gestation was 3.13 (95% CI; 2.74–3.57) and for preterm birth before 28 weeks of gestation 5.96 (95% CI; 4.3–8.3). In women with history of LLETZ, the adjusted OR was 1.95 (95% CI; 1.68–2.25) and 2.88 (95% CI; 1.87–4.43), respectively. Conclusions Women with cervical excision procedure of any kind have significantly increased odds for preterm birth, especially for preterm birth before 28 weeks and before 32 weeks of gestation.
Acute myeloid leukemia (AML) in monozygotic twins is a rare event and, until now, only a few cases have been reported. Due to improved oncological treatment and cancer survival rates, quality of life ...considerations post-treatment have become an important aspect in the treatment regime. The ability to have their own biological children is considered one of the most important indicators of quality of life by cancer survivors. As fertility following oncological treatment is often impaired, fertility preservation methods should be offered to these patients prior to the treatment. Here, we present a very rare case in which we can in vivo observe the impact of oncological treatment on female fertility when applied before and after puberty.
This is a very rare case of concordant AML in monozygotic twin sisters. Twin A became sick at the age of 21 months. She was treated with cytostatic medications and then underwent bone marrow transplantation (BMT), the donor being her twin sister B. After 27 years, she is disease free and has regular periods. After trying to conceive for 4 years, she was seen by an infertility specialist. She underwent hysteroscopic uterine septum removal and laparoscopic enucleation of bilateral paraovarian cysts. Following those procedures, she immediately conceived naturally. Twin B became sick at 15 years of age. She was treated with chemotherapy and cranial radiation and relapsed after 10 years. She then received chemotherapy and had a BMT. Until relapse, she had normal menstrual cycles. After the second treatment she became amenorrhoeic and is now part of an oocyte donation program.
This is a case of AML in monozygotic twins who, after treatment, have completely different reproductive potential. They both received oncological treatment, and one of them conceived conceived naturally while the other suffered premature ovarian failure and is not able to have a biological child. Based on the outcome of this case, it appears that the pre-pubertal state truly serves as protection against ovarian failure.
The aim of this study was to determine whether
maturation (IVM) of immature oocytes after controlled hormonal stimulation of the ovaries could be important in cancer patients to improve their chances ...of conception in the future.
After ovarian stimulation in cancer patients, the number of oocytes and their quality and maturity were compared to control patients with fertility problems in the
fertilization (IVF) program. In both groups of patients, immature oocytes at the developmental stage of germinal vesicle were matured
and the proportion of oocytes that matured
was compared between groups. In a subset of women with fertility problems, intracytoplasmic sperm injection (ICSI) was performed on IVM oocytes to assess their ability to be fertilized and develop into an embryo compared to
matured oocytes in the same cycles and consider the procedure in cancer patients.
In patients with different cancers, the disease did not affect the number and quality of retrieved oocytes. In cancer patients, there was even a significantly lower proportion of immature oocytes than in patients with fertility problems (30.0%
. 43.6%; P < 0.05). However, in patients with cancer, fewer oocytes per patient matured
than in patients with fertility problems (1.39 ± 1.04
. 2.48 ± 1.83; P < 0.05). After ICSI, the proportions of fertilized oocytes and fertilized oocytes developing into an embryo did not differ between oocytes matured
and
in the same cycles.
Oocyte IVM is proving to be a reliable procedure for resolving immature oocytes after controlled ovarian stimulation in cancer patients.
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