First case of dichorionic diamniotic triplet pregnancy after single blastocyst transfer.

Multiple pregnancies are associated with significant maternal, fetal, and neonatal risks, including prematurity, low birth weight, pre-eclampsia, anemia, postpartum hemorrhage, intrauterine growth restriction, neonatal morbidity, and increased neonatal and infant mortality rates. Assisted reproductive technology (ART) treatments should prioritize efforts to reduce such events, resisting patient demand for the transfer of multiple embryos at each transfer to increase success rates. Extended culture, embryo selection, and single blastocyst transfer can mitigate the risk of high-order multiple pregnancies. Intriguingly, elective single-embryo transfer (eSET) greatly reduces, but does not completely eliminate, the likelihood of multiple gestations. The occurrence of monozygotic twinning (MZT) gives rise to identical twins. It is more prevalent in women undergoing in vitro fertilization (IVF) compared with natural conception. In fact, the reported risks of monozygotic twinning in IVF and natural conception are 1.7 and 0.4%, respectively. The factors suspected to increase the risk of MZT in IVF are multiple embryo transfer, micromanipulation, and extended in vitro culture. Determining chorionicity and amnionicity is crucial in the assessment of multiple pregnancies during the first-trimester ultrasound examination. Dichorionic twins result from embryo splitting within 3 days after fertilization, while monochorionic twins occur when the splitting takes place between 4 and 8 days after fertilization. These timings are suggested by observations carried out in natural pregnancies. In ART, there is evidence of dichorionic twins derived from single embryo transfer (SET). Here, we report a case of dichorionic diamniotic triplets after a single blastocyst transfer occurred in our center. To our knowledge, this is the first case documented so far.

Are we choosing the correct FSH starting dose during controlled ovarian stimulation for intrauterine insemination cycles? Potential application of a nomogram based on woman's age and markers of ovarian reserve.

PURPOSE: To evaluate the potential application of a nomogram based on woman's age and ovarian reserve markers as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in intrauterine insemination (IUI) cycles. METHODS: We conducted a retrospective analysis enrolling 179 infertile women undergoing controlled ovarian stimulation (COS), followed by IUI. Each woman received an FSH starting dose according to clinical decision. After collecting data about COS and IUI procedures, we calculated the FSH starting dose according to the nomogram. The main outcomes measured were women's baseline characteristics, COS, and clinical outcomes. RESULTS: The FSH starting dose calculated by the nomogram was significantly lower than the one actually prescribed (p < 0.001), in only 14.8% of the cycles nomogram calculated a higher starting dose. When gonadotropin dose was decreased during COS, and similarly in case of hyper-response (more than two follicles ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (81.8% and 48.8%, respectively). Conversely, when gonadotropin dose was increased during COS and in case of low ovarian response (no follicle ≥ 16 mm retrieved), the FSH starting dose calculated by the nomogram would have been lower in most of the cases (64.7% and 100%, respectively); in these groups median anti-Müllerian hormone (AMH) level was 5.62 ng/mL. CONCLUSIONS: The application of this nomogram in IUI cycles would lead to a more tailored FSH starting dose and improved cost-effectiveness, although in PCOS women, particularly the ones with high AMH, it does not seem adequate.

New neovagina-creating technique on the basis of a fasciocutaneous flap for Müllerian agenesis.

OBJECTIVE: To present a new surgical technique on the basis of an internal thigh fasciocutaneous flap for generating a compliant and sensitive neovagina with preservation of the external genitalia. DESIGN: Video demonstration of the surgical steps. PATIENT(S): An 18-year-old woman with Müllerian agenesis confirmed at ultrasound and magnetic resonance imaging. The residual vagina was 3 cm long and 1.5 cm wide. After counseling by a gynecologist and plastic surgeon, in which all available techniques with pros and cons were exposed, the patient opted for the new technique. The long time required by conservative approaches and the desire to preserve the external genitalia with the chance to have a sensitive vagina guided the choice. INTERVENTION(S): The cul-de-sac of the vaginal stump was incised transversally. A 4-cm-wide and 9-cm-long canal bounded anteriorly by the bladder, posteriorly by the rectum, and superiorly by the peritoneum of Douglas was developed by blunt dissection. Fasciocutaneous flaps of 12 per 5 cm on the anteromedial aspect of the thighs were developed, identifying the vascular-from the pudendal artery-and nervous pedicles. A tunnel between the flap pedicles and neovagina introitus was created between fascia and subcutaneous tissue, detaching the vulvar structures from the ischiopubic ramus. Flaps were tunneled up to the neovagina introitus and sutured together by interrupted suture to form a tube with outside skin. The flaps were transposed into the canal everting the tube to obtain the skin lining the internal neovagina. The inferior margins of the flaps were sutured to the vaginal stump mucosa. No internal stitches were placed. Antibiotic prophylaxis was used during surgery. The entire procedure lasted 6 hours. During the postoperative period, no special positioning or ambulation restrictions were used. MAIN OUTCOME MEASURE(S): Compliance and sensitivity of the neovagina, esthetic result, and perioperative and long-term complications. RESULT(S): The postoperative course was uneventful, with early mobilization. The length of hospital stay was 16 days to allow proper vaginal dilator use; initial daily followed by intermittent use was planned. At a 2-year follow-up, the neovagina was sensitive and patent, allowing sexual intercourse. No complications were reported, and the patient was satisfied with the functional and esthetic result. CONCLUSION(S): The new surgical technique was feasible and effective, preserving the external genitalia and avoiding graft healing and bowel secretion drawbacks without an intra-abdominal surgical step and related risks. However, more cases-2 cases performed to date with similar results-and long-term follow-up are needed to confirm the efficacy. In this regard, the regular use of vaginal dilators and forecast adherence between flaps and the connective tissue of the bladder and rectum are expected to prevent neovagina prolapse without any anchoring to the pelvic structures.

Anti-Müllerian hormone and antral follicle count reveal a late impairment of ovarian reserve in patients undergoing low-gonadotoxic regimens for hematological malignancies.

The impact of cancer therapy on the reproductive potential of patients is increasingly recognized because survival rates of patients have clearly improved in recent years. Different fertility preservation methods, either generally accepted or still experimental, are currently available, and counseling of patients requires a delicate balance between the efficacy and side effects of the proposed method and the characteristics of both the tumor and the therapy. Deeper knowledge of the effects of cancer therapy on the reproductive potential of patients over time is required to identify the most appropriate fertility preservation method. In this paper, we report a case-control study in which female patients who were diagnosed with hematological malignancies and treated with chemotherapy and/or radiotherapy were compared with age-matched controls in terms of ovarian reserve, as measured by ultrasound examination and hormonal status. By stratifying patients for gonadotoxicity of the therapy received and time elapsed from the end of the therapy, we report that patients treated with low gonadotoxic therapies, while being similar to age-matched controls in their ovarian reserve when evaluated within a few years from the end of the therapy, show a clear impairment over longer times. We also report that anti-Müllerian hormone is the most sensitive hormonal parameter in detecting changes in ovarian reserve when compared with follicle-stimulating hormone or inhibin-B. This study stresses the importance of accurate counseling at the time of diagnosis of cancer and emphasizes the risks of infertility with low gonadotoxic therapies that may reduce the reproductive window of survivors.

Normal and abnormal images of intrauterine devices: Role of three-dimensional sonography.

The purpose of this pictorial essay is to describe the diagnostic value of two-dimensional ultrasound (2DUS) and the additional information that three-dimensional ultrasound (3DUS) provides in the assessment of location, type and complications of IUDs.

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk.

OBJECTIVES: Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs. METHODS: A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile). RESULTS: Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001). CONCLUSIONS: In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

A novel de novo partial xq duplication in a girl with short stature, nonverbal learning disability and diminished ovarian reserve - effect of growth hormone treatment and fertility preservation strategies: a case report and up-to-date review.

BACKGROUND: Xq duplication is a rare condition with a very variable phenotype, which could mimic other genetic syndromes involving the long arm of chromosome X. Sometimes short stature and diminished ovarian reserve (DOR) may be present. Treatments with rGH (Recombinant growth Hormon) or with fertility preservation strategies have not been previously described. CASE PRESENTATION: We present the case of a female with a novel de novo Xq partial duplication (karyotype: 46,Xder(X)(qter→q21.31::pter→qter) confirmed by array-CGH analysis. She presented with short stature, Nonverbal Learning Disability, developmental delay during childhood, severe scoliosis, spontaneous onset of menarche and irregular menstrual cycles. AMH (Anti-Müllerian Hormone) allowed detection of a preserved but severely diminished ovarian reserve with a POI (Premature Ovarian insufficiency) onset risk. She was effectively subjected to fertility preservation strategies and rGH therapy. We also reviewed other published cases with Xq duplication, reporting the main clinics characteristics and any adopted treatment. CONCLUSIONS: rGH treatment and cryopreservation in a multidisciplinary approach are good therapeutic strategies for Xq duplication syndrome with short stature and premature ovarian failure.

Functional and endocrine-metabolic oligomenorrhea: proposal of a new diagnostic assessment tool for differential diagnosis in adolescence.

Background To develop a diagnostic assessment tool, using clinical, biochemical and sonographic markers, to help clinicians in the differential diagnosis of functional oligomenorrhea (FO) and endocrine-metabolic oligomenorrhea (EMO). Methods Sixty-two adolescents with oligomenorrhea without evident hormonal imbalances or severe energy deficit were selected. They were divided into two groups (EMO and FO) and they all underwent the following assessment: physical examination (height, weight, presence of hirsutism or acne), blood exams and transabdominal ultrasonography. The biochemical markers included: hemoglobin, thyrotropin stimulating hormone (TSH), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), free (FT) and total testosterone (TT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG). Uterine and ovarian volume, ovarian morphology, endometrial thickness and pulsatility index (PI) of uterine arteries were evaluated with ultrasound. Results Body mass index (BMI), hemoglobin, LH levels and LH/FSH ratio were significantly higher in women with EMO than in those with FO. Increased androgens values were found in the EMO group, but only A and FT were significantly different (p=0.04). Ovarian volume and uterine artery PI were the only ultrasound features significantly different, with higher values in the EMO population (p<0.05). Considering these variables, with a receiving characteristic operating curve, new cut-offs were calculated, and a diagnostic assessment tool elaborated (area under curve [AUC] 0.88, specificity 99%, sensibility 59%, p<0.001]. Conclusions This diagnostic tool, specific for adolescents, could be useful in the management of oligomenorrhea. Recognizing and distinguishing EMO and FO is very important in order to establish an appropriate treatment and a correct follow-up.

Clinical application of a nomogram based on age, serum FSH and AMH to select the FSH starting dose in IVF/ICSI cycles: a retrospective two-centres study.

OBJECTIVE: To externally validate a nomogram based on ovarian reserve markers as a tool to optimize the FSH starting dose in IVF/ICSI cycles. STUDY DESIGN: A two-centres retrospective study including 398 infertile women undergoing their first IVF/ICSI cycle (June 2013-June 2014). IVF data were retrieved from two independent IVF centres in Italy (San Raffaele Hospital, Centre 1; Verona Hospital, Centre 2). A central lab for the routine measurement of AMH and FSH was used for both centres. All women were treated based on physical and hormonal characteristics according to locally adopted protocols. The nomogram was then retrospectively applied to the patients comparing the calculated starting dose to the one actually given. RESULTS: In Centre 1, 64/131 women (48.8%) had an ovarian response below the target. While 45 of these patients were treated with a maximal FSH starting dose (≥225 IU), n=19/131 (14.5%) were treated with a submaximal dose. The vast majority of them (n=17/19) would have received a higher FSH starting dose by using the nomogram. Seventeen patients (n=17/131) had hyper response and about half of them would have been treated with a reduced FSH starting dose according to the nomogram. In Centre 2, 142/267 patients (53.2%) had an ovarian response below the target. While 136 of these were treated with a maximal FSH starting dose (≥225 IU), n=6/267 were treated with a submaximal dose. The majority of them (n=5/6) would have received a higher FSH starting dose. Thirty-two (n=32/267) patients had hyper response and more than half of them would have been treated with a reduced FSH dose. CONCLUSION: In both Centres, applying the nomogram would have resulted in more appropriate FSH starting doses compared to the the ones actually given based on clinicians choices. The use of an objective algorithm based on patient's age, serum FSH and AMH levels may thus be an effective advice on the selection of the tailored FSH starting dose. Hence, the use of this easily available nomogram could increase the proportion of patients achieving the optimal ovarian response.