Can the endometrioma be an obstacle to complete oocyte retrieval in IVF cycles? A retrospective study.

OBJECTIVE: The study aimed to evaluate the utility and safety of ancillary maneuvers during oocyte retrieval for patients with endometrioma that makes ovum pick-up hard due to poor ovarian surgical accessibility. PATIENTS AND METHODS: Cases of 251 women with ovarian endometriomas undergoing in vitro fertilization (IVF) in our infertility unit were retrospectively analyzed to evaluate the clinical IVF cycle outcomes after oocyte retrieval. Controls (n = 251) were age-matched women without endometriomas who underwent an uncomplicated oocyte retrieval. RESULTS: No statistically significant differences were observed between groups except for the number of oocytes retrieved, which was higher in the control group than in the group of women with endometrioma. On the contrary, there were no differences between the experimental groups in the fertilization rate and number of embryos, and neither were there in the pregnancy and live birth rate. Moreover, the surgical complications were infrequent and similar between the two analyzed groups. Accidental or voluntary endometrioma punctures were not accompanied by increases in the risk of a pelvic infection. CONCLUSIONS: In conclusion, patients with endometrioma can undergo high-performance oocyte recovery procedures thanks to safe accessory maneuvers during the ovum pick-up.

Obesity does not increase the risk of side effects and complications of egg retrieval: delaying oocyte retrieval in obese patients is not a good strategy.

OBJECTIVE: Obesity is one of the main concerns for public health and is becoming an increasingly widespread problem worldwide. Women are more likely to require a cesarean section and have a longer hospital stay after delivery. Excess body weight can interfere with ovulation and make it more difficult for embryos to implant in the uterus. A high body mass index (BMI) has controversial effects on the outcomes of medically assisted reproduction treatments (IVF) and, if careful counseling is not performed, medical-legal risks may be incurred. While some researchers argue that obesity does not particularly affect ART outcomes, other studies claim that a high BMI does not interfere with embryonic development. Both the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) has stated that there is no clear evidence supporting a BMI limit for IVF treatment and that each patient should be evaluated on an individual basis. The purpose of our study was to evaluate whether performing in vitro fertilization on these patients increases the risk of medical, surgical, and anesthetic complications of oocyte retrieval. PATIENTS AND METHODS: From January 2011 to December 2022, all patients with BMI higher than 25 were enrolled in the study (n=766). Complications and risks related to oocyte retrieval were evaluated, and patients were divided according to BMI groups. RESULTS: With the one-way ANOVA test, all groups were compared with the control group, and none showed statistically significant differences, only the number of produced embryos in the BMI group between 30-34.9 was lower and statistically significant. CONCLUSIONS: Only one study has analyzed these aspects, mainly focusing on the need for anesthesia drugs and any related complications, and the same author reported greater difficulty in performing oocyte retrieval. The same study recorded an increase in incomplete oocyte retrievals. Our work does not confirm any of these impressions.

Evaluation of the ideal vaginal Progesterone effectiveness doses for luteal support in embryo thawing cycles after endometrial preparation without using the GnRh analogue.

OBJECTIVE: Frozen-thawed embryo transfer (FET) cycles require the use of luteal phase support (LPS) for supporting implantation, endometrial and embryo maturity. Individualized LPS should be chosen according to the used endometrial preparation protocol. The aim of the study was to analyze the effectiveness of two different vaginal Progesterone doses for women who underwent FET cycle and the same endometrial preparation without using the GnRh analogue. PATIENTS AND METHODS: 607 women who underwent FET cycle were included in the study. 305 patients received luteal support with 600 mg/day vaginal Progesterone and 302 patients were treated with 800 mg/day of vaginal Progesterone. RESULTS: In the 800 mg/day group, the mean serum Progesterone concentration on the day of embryo transfer was higher than in the 600 mg group (14.00±6.18 ng/mL and 12.22±5.39, respectively, p < 0.001). Moreover, human chorionic gonadotrophin (hCG) positive and ongoing pregnancy rates were higher in the group of patients who received LPS with 800 mg/day of Progesterone than in the group of patients treated with 600 mg/day of Progesterone.  CONCLUSIONS: In patients undergoing FET cycles following endometrial preparation made without previously using the GnRh analogue, 800 mg doses of vaginal Progesterone as LPS improve reproductive outcomes.

Effects of a combination of resveratrol and alpha-lipoic acid on body weight and adipose composition in women with PCOS: a preliminary pilot study.

OBJECTIVE: Polycystic ovary syndrome is associated with reproductive and metabolic dysfunction; in fact, treatment aims in PCOS focus on optimizing healthy weight, improving underlying hormonal disturbances, preventing future reproductive and metabolic complications, and improving quality of life. PATIENTS AND METHODS: This pilot study considered 8 overweight females (BMI > 30) in reproductive age with PCOS. Patients were treated with a galenical preparation mixture containing resveratrol and alpha-lipoic acid in association with vitamin D, B and folic acid for 12 weeks, after which anthropometric assessment was conducted. RESULTS: After 12 weeks of treatment, BMI, anthropometry and bioimpedance parameters were all reduced in the treated patients compared to baseline. CONCLUSIONS: The present nutraceutical combination resulted beneficial for improving the metabolic profile of women with PCOS, paving the way for new nutraceutical strategies for the management of metabolic disturbances in PCOS.

Curcumin and Teupolioside attenuate signs and symptoms severity associated to hirsutism in PCOS women: a preliminary pilot study.

OBJECTIVE: Hirsutism affects 5-15% of women of reproductive age, with approximately 80% of these women having polycystic ovary syndrome (PCOS). The etiopathogenesis of PCOS remains unclear, the clinical characteristics of PCOS include hyperandrogenism, generally manifested as hirsutism and acne, and both these clinical symptoms are treated with oral contraceptive pills (OCPs), topical medications or antiandrogens. Curcumin (diferuloylmethane) and Plant sterols, such as a phenylpropanoid glycosides of Ajuga reptans, known as Teupolioside, have attracted considerable attention due to their pharmacological properties. Taking into consideration wide-ranging pharmacological and biological properties and the safety of herbal extracts, we proposed a combination of curcumin and teupolioside to evaluate the anti-androgenic properties in women with PCOS and clinical signs of hyperandrogenism. PATIENTS AND METHODS: Six hyperandrogenic PCOS women with a hirsutism score (HS) > 20, according to Ferriman-Gallwey scoring system, were involved in the study. These women were treated with a galenical preparation mixture containing curcumin and teupolioside and clinical features were assessed after 12 weeks. RESULTS: The nutraceutical combination containing curcumin/teopolioside ameliorated clinical manifestations associated to hyperandrogenism in women with PCOS after a 12-weeks treatment. CONCLUSIONS: This pilot study suggests that a curcumin/teopolioside nutraceutical combination is beneficial for improving various clinical manifestations associated to abnormal hormonal parameters in PCOS women, as well as signs and symptoms associated to hyperandrogenism.

In patients with isthmocele undergoing IVF, the risk of ectopic pregnancy on the cesarean scar is reduced only if the ultrasound-guided transfer is performed on day 5 - A retrospective case-control study.

OBJECTIVE: The study aimed to demonstrate that the risk of Cesarean Scar Pregnancy (CSP) for patients with isthmocele decreases when the embryo transfer is performed on day 5 at the blastocyst stage. PATIENTS AND METHODS: From January 2014 to December 2021, 167 patients who previously had an IVF treatment and delivered by cesarean section, were selected. The isthmocele was found in 98 of them. Firstly, we evaluated whether the isthmocele increases the risk of CSP. Subsequently, we investigated the possible correlation between the risk of the CSP with the day of the embryo transfer. Hence, the selected patients were divided into two groups: Group A where the embryo transfer was performed at the cleavage stage on day 3 and Group B where the embryo was transferred at the blastocyst stage on day 5. RESULTS: The outcomes show that the isthmocele does not seem to increase the risk of CSP, while the embryo transfer on day 3 increases its rate. CONCLUSIONS: When the isthmocele is diagnosed, according to our results, an embryo transfer on day 5 at the blastocyst stage seems to minimize the risk of the CSP.

The abortion rate in trans-myometrial eggs retrieval is the same as in classical transvaginal retrieval.

OBJECTIVE: This study compares the miscarriage rate of pregnancies after trans-myometrial eggs retrieval to transvaginal eggs retrieval. PATIENTS AND METHODS: In the period between January 2004 and December 2020, 13,323 egg retrievals were carried out. In 699 cases, the ovaries were unreachable. Alternative maneuvers were performed to solve this problem, but despite this, in 132 patients the technique of trans-myometrial sampling had to be used. 26 patients were excluded from the study, because of the inclusion criteria, and therefore two groups of 106 patients were selected, Group A and Group B (control). RESULTS: In the comparison between the two groups, there were no statistically significant differences in abortion rates, pregnancy rates and complications after the technique. CONCLUSIONS: This study shows that the abortion rate in trans-myometrial oocyte retrieval does not change when compared to classic retrieval, despite the sampling needle completely crossing the myometrium. Furthermore, the pregnancy rate and the complication rate do not appear to have worsened with this technique.

Increased bioavailability of Vitamin D improved pregnancy outcomes in in vitro fertilization cycles, only in patients over 36 years: a cross-sectional study.

OBJECTIVE: Vitamin D (VitD) is a secosteroid hormone showing both antiproliferative and immunomodulatory effects. Its involvement in placental steroidogenesis and endometrial decidualization even plays a role in other gynecological functions, including assisted reproductive technology (ART). However, controversial data have been reported on its implication in pregnancy outcomes during In Vitro Fertilization (IVF) programs. In order to elucidate the VitD role in ART success, we evaluated serum and follicular fluid (FF) VitD levels in infertile women concerning the pregnancy rate. PATIENTS AND METHODS: In our IVF center, 446 patients, under the age of 42 years old,  were evaluated in the period between January 2018 and December 2019. It is here important to clarify that, in order to respect the exclusion criteria, only 103 of them were enrolled for the study concerning the VitD evaluation in serum and follicular fluid at the time of the egg retrieval. This took place both in 34 pregnant patients (Group 1) and 69 non-pregnant ones (Group 2). Furthermore, the collection of these data gave us the opportunity to assess a possible correlation between the VitD levels and the achievement of pregnancy in the performed IVF cycles. RESULTS: The studied group included 103 eligible women. The average age for Group 1 was 33.12 ± 3.72 yrs whereas 33.72+3.99 yrs (p=0.467) for Group 2. The main differences were observed concerning follicle numbers of 17-21 mm (p=0.0043), the number of retrieved oocytes (p=0.0207), as well as the number of mature oocytes (p=0.0233) among the different groups. Different reference ranges, established according to the pregnancy outcomes, revealed that pregnant women with >36 yrs showed significantly higher levels of VitD. CONCLUSIONS: Increased serum and FF-VitD levels in women undergoing IVF with age ≥36 yrs, were significantly associated with a favorable outcome to achieve and carry on with the pregnancy.

Intrapartum sonography of fetal head in second stage of labor with neuraxial analgesia: a literature review and possible medicolegal aftermath.

OBJECTIVE: Intrapartum ultrasound (IU) is a valid support to obstetric management of fetal head progression in the second stage of labor in nulliparous with neuraxial labor analgesia (NLA). Nulliparous with NLA may have a prolonged the second stage of labor. The aim of this literature review was to evaluate the mode of delivery, as well as maternal and fetal morbidities associated with missed progression of fetal head detected with IU in the second stage of labor in nulliparous women with NLA. MATERIALS AND METHODS: The literature review was performed using PubMed, Cochrane, Medline, EMBASE, Scopus, Google Scholar and book chapters searches to identify relevant articles from 2001 to 2019, evaluating the mode of delivery and morbidities of the second stage of labor. Search terms used were "Intrapartum ultrasound", "dystocia", "prolonged labor", "neuraxial analgesia", "persistent occiput posterior position", "asynclitism", "second stage of labor", "medico-legal aftermath". Prolonged second stage was defined as three hours and more. Retrospective case series of women with prolonged second stage of labor with NLA were identified. The primary outcome was the incidence of operative vaginal delivery (OVD) and cesarean delivery (CS). RESULTS: The use of NLA may determine a prolonged second stage of labor (PSSL). IU when compared to the traditional vaginal digital examination (VDE) demonstrated the highest degree of diagnostic accuracy. CONCLUSIONS: The use of IU during NLA can aid in the diagnosis of fetal head progression, station or malposition and malrotation, alerts obstetrician on the possibility of dystocic labor, indicating to stop the drug administration in NLA and shift to OVD or CS. Extending the second stage of labor beyond current American College of Obstetricians and Gynecologists (ACOG) recommendations is beneficial. The ISUOG guidelines recommended the clinical application of IU to diagnose the persistent occiput posterior position (POPP) and asynclitism (A) in dystocic labor and produce photographic evidence of the case. Maternal and neonatal complications, medicolegal consequences and litigation can decrease if the IU device is used as good practice.

Does episiotomy always equate violence in obstetrics? Routine and selective episiotomy in obstetric practice and legal questions.

OBJECTIVE: The study's main goal is to figure out whether episiotomy, a widely applied invasive procedure, may constitute a determining factor of liability for practitioners according to the standards of obstetric violence. MATERIALS AND METHODS: The authors have aimed to analyze laws and documentation issued on the matter by sovereign states, statements and remarks from International health organizations, in addition to scientific article available on the main search engines (PubMed, Scopus, Google Scholar) and legal databases (Lexis, Justia). RESULTS: The body of research has highlighted the existence of a wide-ranging agreement as to routine episiotomy, deemed to be a scientifically unfounded procedure, and which should, therefore, be avoided. By virtue of that, routine episiotomy might easily give rise to charges and liability for doctors and midwives alike; likewise to claims may stem from a failure to perform an episiotomy when it was actually needed. CONCLUSIONS: Unlike routine episiotomy, selective episiotomy is far more unlikely to cause charges of obstetric violence against operators. Unfortunately, the criteria in order to establish when a selective episiotomy is indicated are far from consistent and would require an additional effort on the part of scientific societies towards a more clearly defined and shared description.

High progesterone levels on the day of HCG administration do not affect the embryo quality and the reproductive outcomes of frozen embryo transfers.

OBJECTIVES: The aim of this study was to evaluate the impact of pre- mature progesterone rise on the day of human chorionic gonadotropin (hCG) administration on the outcome of in vitro fertilization (IVF) of frozen embryo transfer (FET) cycles using cleavage-stage embryos. METHODS: This was a retrospective, cohort study of 131 ovarian stimulation cycles followed by cleavage-stage frozen embryo transfers. The first group consisted of women undergoing FET due to premature luteinization during controlled ovarian stimulation (n = 56, P ≥1.2 ng/ml). The controls were represented by women undergoing FET not complicated by high progesterone levels at induction (n = 75, P < 1.2 ng/ml). For both groups, the progesterone was measured on the day of hCG administration and the fertilization rate, cleavage rate, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and Top-Quality Embryos (TQE) rates were compared. RESULTS: The increase of progesterone in patients of the Group A had no significant effects on the number of oocytes retrieved or available for the insemination. The fertilization rate, cleavage rate and implantation rates, as well as the clinical pregnancy rate and ongoing pregnancy were very similar in both study groups. The analysis of TQE rates between the two groups indicated a roughly comparable result. CONCLUSIONS: The results of this study showed that progesterone elevation on the day of hCG administration did not affect the outcomes of IVF with frozen embryos at cleavage stage. This study therefore confirms that for patients with high progesterone levels the right way to obtain a healthy pregnancy should be to delay the embryo transfer at a successive FET cycle, not associated with the ovarian stimulation.

Can trans resveratrol plus d-chiro-inositol and myo-inositol improve maternal metabolic profile in overweight pregnant patients?

OBJECTIVE: To investigate the effect of trans-resveratrol from Polygonum cuspidatum/magnesium hydroxide complex, trademark Revifast®, plus D-chiro-inositol (DCI) and Myo-inositol (MI) during spontaneous pregnancies in overweight patients in a pilot study. STUDY DESIGN: A one-year, prospective, randomized, double-blinded, placebo-controlled single center clinical study was carried out on overweight pregnant women. 110 patients were randomized in 3 groups to receive: Revifast® with DCI/MI (group I), DCI/MI alone (group II) or control group (group III) for 30 and 60 days. The main outcomes were to explore the lipid profile (total cholesterol, LDL, HDL, TG) and glucose levels, after 30 and 60 days of therapy. RESULTS: No difference in systolic and diastolic parameters among 3 groups during study. All blood chemistry parameters improved compared to placebo at 30 days already, but significantly to 60 days, respect placebo. By comparing the two treatment groups, group I demonstrates significantly improved lipid and glucose parameters than group II, which are at 30 to 60 days of treatment. CONCLUSIONS: The supplementation of Trans-resveratrol, Revifast® in addition to DCI/MI in overweight pregnant woman with an elevated fasting glucose improves glucose levels, Total Cholesterol, LDL and TG.

2014-2017. How medically assisted reproduction changed in Italy. A short comparative synthesis with European countries.

More than ten years after law n. 40 of February 19, 2004 became effective, regulation on medically assisted reproduction has dramatically changed outlook. The authors report on the steps that led to these changes through Courts' rulings, the Supreme Court's verdicts and the European Court of Human Rights' decisions, as well as ministerial regulations and guidelines concerning medically assisted reproduction. The aforementioned jurisprudential evolution was set to reach a new balance between the embryo's right to its own dignity and the woman's right to health and freedom of self-determination in reproduction. No court ruling denies that embryos have also to be safeguarded. In fact, there are still numerous prohibitions, including using embryos for experimental purposes. Judges aim primarily at avoiding that embryos' rights overcome the right to parenthood. The authors review the legislation of the various European countries: some have adopted a legislation to regulate medically assisted reproduction, while others have developed in this field some recommendations or guidelines. This is why they call for enactment of a European law governing the implementation/operational methods of medically assisted reproduction in order to avoid the scourge of procreative tourism to countries that have a more permissive law.

Asymptomatic isthmico-cervical uterine perforation with IUD - our experience and literature review.

PURPOSE: The study aim was to report an unusual case of a misplaced IUD in isthmico-cervical region causing partial uterine perforation and discuss literature data regarding such a condition. CASE REPORT: A 50-year-old women was referred to the present institution for IUD extraction. She was diagnosed with spontaneously misplaced IUD located in isthmico-cervical region of the uterus causing partial perforation. The time of dislocation was unknown, as she was completely asymptomatic for ten years after IUD application. More-over, she had no risk factors for device misplacement. The removal of IUD was uneventful. CONCLUSION: Isthmico-cervical misplacement of IUD, although rare, can occur at any time and can be asymptomatic. Thus, women with IUD should be annually checked-up in order to prevent possible IUD complications.

Missense mutations in exon 2 of the MED12 gene are involved in IGF-2 overexpression in uterine leiomyoma.

Uterine leiomyoma (UL), the most common benign tumour found in females, is associated with many recurrent genetic aberrations, such as translocations, interstitial deletions and specific germline mutations. Among these, mutations affecting exon 2 of the mediator complex subunit 12 (MED12) gene are commonly detected in the majority of ULs. Mutational analysis of the MED12 gene, performed on 36 UL samples, revealed that 12 leiomyomas (33.4%) exhibited heterozygous missense mutations in codon 44 of exon 2 of the MED12 gene, four leiomyomas (11.1%) showed internal in-frame deletions, and two leiomyomas (5.5%) exhibited deletions involving intron 1-exon 2 junction, which caused a predicted loss of the splice acceptor. No mutations were detected in uterine myometrium (UM) and pseudocapsule (PC) samples, including those from women with a MED12 mutation in UL. These data showed that the PC is a healthy tissue that surrounds the UL to maintain UM integrity. Analysis of insulin-like growth factor 2 (IGF-2) and collagen type IV alpha 2 (COL4A2) mRNA expression levels in the same set of ULs revealed that only those with MED12 missense mutations expressed significantly higher levels of IGF-2 mRNA. In contrast, MED12 gene status does not appear to affect mRNA expression levels of the COL4A2 gene. On the basis of this finding, we suggest that the MED12 status stratifies the ULs into two mutually exclusive pathways of leiomyoma genesis, one with IGF-2 overexpression and the other with no IGF-2 activation. The occurrence of IGF-2 overexpression could be therapeutically targeted for the non-surgical treatment of leiomyomas.