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RUOLO DI VITAMINE E MICRONUTRIENTI NELLA DIAGNOSI E CURA DELL¿INFERTILITÀ DI COPPIA
Full text linkIntroduction
Maternal nutritional status is considered by many Authors to be closely related to the reproductive success. The human reproductive process, from a probabilistic point of view, is ineffective and, in spite of the scientific research progressively adding elements to the understanding of reproductive failure, the mechanisms underlying the failure to conceive, the embryonic arrest and the occurrence of neonatal malformations remain largely unknown. In this area, nutrition and micronutrient status represent an important research target for two main aspects: 1) nutrition as a cause of reproductive failures 2) nutritional status as a key variable influencing the chance of success in assisted reproduction procedures.
Aim
This PhD project has been focused on the study of specific analytes in infertile couples, with particular reference to the probability of success in terms of pregnancy given particular conditions of deficiency / insufficiency.
Methods and results
The project was conducted at the “Infertility Unit” of the Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico of Milan in collaboration with the Department of Clinical Sciences and Community at the University of Milan, in order to assess the baseline status of specific micronutrients and place it in relation to the chances of getting pregnant using assisted reproductive technologies. Evaluated analytes (vitamin D, folate, homocysteine, vitamin B12, vitamin E, vitamin E, iron and ferritin) were selected based on their involvement in the reproductive process. Subjects were recruited from couples treated for infertility; in the study of serum levels in infertile compared to subfertile women, recruitment was performed among pregnant women during the first trimester prenatal screening (U.O. Obstetrics and Gynecology). Several outcomes were evaluated using case series disjointed or partially overlapping. In particular, the PhD work was divided into 5 main studies, the characteristics of which are summarized in the following scheme:
Study: 1
Analyte: Vitamin D
Main Outcome: Pregnancy Rate in in vitro fertilization cycles
Design: Prospective cross-sectional
Subjects: 480 women in infertile couples
Main results: Women with 25 (OH) D ≥ 20 ng / ml are more likely to have a pregnancy compared to those with 25 (OH) D insufficiency.
Adjusted OR = 2.15 (95% CI: 1.23-3.77) (p = 0 .007).
Study: 2
Analyte: Vitamin D
Main Outcome: Concordance of serum levels between partners
Design: Prospective cross-sectional
Subjects: 103 infertile couples
Main results: 71% of infertile couples showed concordance between a condition of sufficiency or insufficiency between partners. This frequency is higher than expected in case of random assortment between partners(p = 0.007).
Study: 3
Analyte: Vitamin D
Main outcome: Serum levels in fertile versus subfertile women
Design: Prospective case-control
Subjects: 73 cases and 73 controls
Main results: Vitamin D status does not affect the natural fertility. OR for subfertility (time to pregnancy> 12 months) in women with low vitamin D = 0.85 (95% CI: 0.44-1.62)
Study: 4
Analytes: Folate, Homocystein, Vitamin B12, Vitamin A, Vitamin E, Iron, Ferritin
Main outcome: Rate of insufficiency
Design: Prospective cross-sectional
Subjects: 269 women in infertile couples
Main results: Only a minority of women attending an Infertility Unit show pre-gestational values of intraerythrocytic folate (12%) and vitamin B12 (44%)
Study: 5
Analytes: Folate, Homocystein, Vitamin B12
Main outcome: Pregnancy Rate in in-vitro fertilization cycles
Design: Prospective cross-sectional
Subjects: 209 women in infertile couples
Main results: Women with serum and intraerythrocytic folate in the third tertile of concentration are more likely to obtain a clinical pregnancy in in-vitro fertilization cycles. OR = 2.8 (1.5-5.3) and 2.1 (1.1-4.0), respectively.
Conclusion
Infertile couples, and women in particular, have a high incidence of vitamin D, folate and vitamin B12 insufficiency. This condition, with specific regards to vitamin D and folate, while represents a risk factor for complications of a possible pregnancy, is strongly associated with a lower success rate of in-vitro fertilization. Further studies are needed to identify possible causal relationships between insufficiency of specific analytes and reproductive failure. The demonstration of a benefit in terms of pregnancies per in-vitro fertilization cycle through the use of supplementation of micronutrients would be a result of huge interest because it would represent the rationale for an effective, economic and easy intervention, to be implemented in an area where progress is slow and mostly dependent on expensive technologies
Closed versus open vitrification systems for human oocytes and embryos : a mini-review
No full textVitrification is an established and successful technique for preserving human oocytes and embryos. It can be achieved either by direct (open systems) or indirect (closed systems) contact with liquid nitrogen and there is not a consensus on the optimum vitrification protocol. Scientific societies agree that there are no particular concerns regarding vitrification other than direct contact with a non sterile product. Moreover, European directives pose the need for aseptic procedures as a critical point. Therefore, several strategies have been developed in order to avoid the risk of contamination, including closed devices and liquid nitrogen sterilization. There have been concerns with closed vitrification devices that a reduction in cooling rate compared to open vitrification systems due to thermal insulation of samples would cause ice crystal formation resulting in impaired results. It has been proposed that a correct exposure to cryoprotective agents before closed vitrification and a high warming rate can adequately compensate the reduction in cooling rates. This reduction in cooling rate can also be prevented with direct plunging of samples in sterile liquid nitrogen followed by hermetical cryostorage (semi-closed system). Studies comparing different protocols suggest that aseptic vitrification is an effective strategy both for embryos and oocytes
The impact of thyroid autoimmunity on IVF/ICSI outcome : a systematic review and meta-analysis
No full textBACKGROUND: Thyroid autoimmunity (TAI) is the most frequent autoimmune condition and the first cause of thyroid dysfunction
among women of reproductive age. Notably, it has been associated with adverse obstetric outcomes during all trimesters of pregnancy.
Furthermore, since most studies show an increased prevalence of TAI among women attending infertility clinics, a detrimental impact of
this condition on natural fertility and on the rate of success of assisted reproductive techniques has been suggested. However, to date, the results have been inconsistent.
OBJECTIVE AND RATIONALE: The objective of this study was to define the relation between TAI per se and the outcome of in vitro
fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.
SEARCH METHODS: A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all
the comparative studies published from January 1990 to November 2015 in the English language literature on IVF/ICSI outcome in women with and without TAI, using combinations of the medical subject heading terms ‘thyroid autoimmunity’, ‘thyroid autoantibodies’, ‘IVF’, ‘ICSI’, ‘pregnancy’, ‘miscarriage’ and ‘delivery’. The primary outcome was live birth rate (LBR). Our secondary outcomes were number of oocytes retrieved (NOR), fertilisation rate (FR), implantation rate (IR), clinical pregnancy rate (CPR) and miscarriage rate (MR). We also extracted data on mean age and basal serum concentrations of thyroid stimulating hormone (TSH) and performed a meta-regression analysis to assess the effect of these two covariates on CPR and MR.
OUTCOMES: We selected 12 studies for the meta-analysis. Six of the included studies were prospective cohort studies, and six
were retrospective cohort studies. Compared with women with negative TAI, women with positive TAI had a lower LBR (odds ratio
(OR) 0.73; 95% confidence interval (CI) [0.54–0.99]; P = 0.04; 9 studies; 4396 women; I2 = 41%), a higher MR (OR 1.44; 95%
CI [1.06–1.95]; P = 0.02; 12 studies; 4876 women; I2 = 35%), a similar CPR (OR 0.90; 95% CI [0.77–1.06]; P = 0.22; 12 studies;
4876 women; I2 = 7%), a similar number of oocytes (standardized mean difference [SMD] 0.10; 95% CI [−0.09 to 0.29]; P = 0.28;
5 studies; 1506 women; I2 = 47%), a similar FR (OR 1.11; 95% CI [0.97–1.27]; P = 0.13; 3 studies; 1082 women; I2 = 0%) and a similar
IR (OR 0.98; 95% CI [0.73–1.32]; P = 0.91; 2 studies; 918 women; I2 = 0%). Both mean age (SMD 0.96; 95% CI [0.66–1.27];
P < 0.00001; 9 studies; 3256 women; I2 = 85%) and serum TSH (SMD 0.24; 95% CI [0.15–0.34]; P < 0.00001; 6 studies; 2098
women; I2 = 59%) were higher in women with TAI. However, neither of these two covariates were significantly associated with CPR
or MR.
WIDER IMPLICATIONS: TAI does not impact on IVF/ICSI outcome in terms of NOR and likelihood of fertilisation, implantation and
clinical pregnancy. On the contrary, the presence of thyroid autoantibodies may have a detrimental effect on the course of a pregnancy,
determining an increased risk of miscarriage and a decreased chance of live birth. However, given the possible modifying effects of age and serum TSH, further evidence is warranted prior to drawing inferences on causality
Human parthenogenetic stem cells
No full textThe invention provides a method for establishing pluripotent cell lines from human parthenotes, the uses of said cell lines for producing differentiated cells or tissues and for therapeutic applications especially in regenerative medicine
Parthenogenetic activation: biology and applications in the ART laboratory
No full textParthenogenesis is a reproductive strategy typical of lower species where a female gives birth to offsprings without a paternal contribution. On the contrary, parthenogenesis is not a form of natural reproduction in mammals even if mammalian oocytes, under appropriate stimuli, can undergo to parthenogenetic activation. This review describes the biological mechanisms regulating parthenogenetic activation in mammals and illustrates the fundamental differences between embryos and parthenotes. Ethical, legal and political concerns on the value of human embryos regulate and limit human embryological studies founded on the widespread belief that human embryos should not be created and studied for research purposes only. Based on the differences between parthenotes and embryos the use of parthenogenesis is proposed as an experimental tool to investigate embryo development which may solve many of the ethical concerns associated with the use of human embryos for experimental purposes. Examples of the possible uses of parthenotes in many field of research such as in vitro assays aimed to study some aspects of assisted reproductive technologies (ART), toxicology or stem cell are described and their validity is discussed
Reply: The impact of thyroid autoimmunity on IVF/ICSI outcome: re-evaluation of the findings
No full text
Postoperative hormonal therapy after surgical excision of deep endometriosis
No full textThe clinical management of women with deep peritoneal endometriosis remains controversial. The debate focuses mainly on the precise role of hormonal medical treatment and surgery and on the most suitable surgical technique to be used. In particular, considering the risks of second-line surgery, prevention of recurrences after first-line surgery is a priority in this context. Post-surgical medical therapy has been advocated to improve the effectiveness of surgery and prevent recurrences. However, adjuvant therapy, i.e. a short course of 3-6 months of hormonal therapy after surgery, has been proven to be of limited or no benefit for endometriosis in general and for deep peritoneal endometriosis in particular. On the other hand, two cohort studies suggest a beneficial effect of prolonged hormonal therapy after surgery for deep endometriosis. Even if this evidence is too weak to confidently advocate systematic administration of prolonged medical therapy after surgery, we argue in favour of this approach because of the strong association of deep endometriosis with other disease forms. In fact, women operated on for deep endometriosis may also face recurrences of endometriomas, superficial peritoneal lesions and pelvic pain in general. The demonstrated high effectiveness of prolonged postoperative therapy for the prevention of endometriomas' formation and dysmenorrhea recurrence should thus receive utmost consideration in the decision-making process
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