Francesca Filippi

PTSD, risk factors, and expectations among women having a baby: a two-wave longitudinal study.

Introduction. The aim of the study was to evaluate the incidence of chronic post-traumatic stress disorder (PTSD) after childbirth in relation to pre-partum variables (personality characteristics, anamnestic risk factors) and intra-partum obstetrical and neonatal variables. Since expectations before an event could modify the perceptions, reactions, and satisfaction afterward, the representations of the idealized delivery were carefully analyzed. Moreover, the real and desired help perception from physicians and family members were separately considered during pregnancy and after delivery in relation to PTSD. Method. The study was carried out submitting a questionnaire to pregnant women twice: firstly when women were in their 38 ≪ 42 gestational week (Time 1) and secondly after 3–6 months from childbirth (Time 2). 93 women were recruited at a University City Hospital in Milan, Italy. PTSD subscales, depression, and anxiety levels were also assessed. Results. 2.4% of women had a complete PTSD, while 32.1% of them resulted in having one or two positive subscales of symptoms: 15.5% (N = 13) had a positive intrusion subscale, 25.0% (N = 21) had a positive arousal subscale, while only 3.6% (N = 3) had a positive avoidance subscale. Pre-delivery depression influences PTSD, but only for the intrusion subscale. Pre-delivery physical risk factors are linked to PTSD on the avoidance subscale. At Time 2 depression and PTSD are often present simultaneously. Given the high percentage of healthy newborns, intra-partum obstetrical variables do not seem to influence PTSD. High trait anxiety distinctively coexists with a specific expected delivery and a ‘deception’ in desired and real support from professionals. Conclusions. Childbirth is a risk condition for PTSD, depression during pregnancy influences the intrusion subscale, while having physical problems influences the arousal subscale. Expectations and support are modulated by the anxiety levels and they are not directly related to chronic PTSD.

Fertility preservation in women with endometriosis: for all, for some, for none?

The increasing confidence with the techniques of oocyte and ovarian cortex freezing has prompted their potential use for patient categories other than those at risk of early menopause due to cancer treatments. Women affected by every iatrogenic or pathologic condition known to compromise ovarian function severely have been considered as potential candidates for fertility preservation. Among them, women with endometriosis may represent a particularly suitable group since they are at increased risk of premature ovarian exhaustion and about half of them will experience infertility. Based on the currently available notions on the intricate relationships between endometriosis, infertility and damage to the ovarian reserve, we speculate that fertility preservation may be of interest for women with endometriosis, in particular for those with bilateral unoperated endometriomas and for those who previously had excision of unilateral endometriomas and require surgery for a contralateral recurrence. Young age at diagnosis may be an independent but pivotal additional factor to be taken into consideration in the balance of the pros and cons of fertility preservation. On the other hand, we argue against the introduction of fertility preservation for endometriosis in routine clinical practice. To date, only few cases have been reported and there are insufficient data for robust cost-utility analyses. It is noteworthy that endometriosis is a relatively common disease and systematically including affected women in a fertility preservation program would have profound clinical, logistic and financial effects. More clinical data and in-depth economic analysis are imperative prior to recommending its routine use.

Ovarian endometriomas and oocyte quality: insights from in vitro fertilization cycles

OBJECTIVE To evaluate whether the presence of endometriomas affects ovarian function. DESIGN Prospective cohort study. SETTING Infertility unit of an academic setting. PATIENT(S) Twenty-nine women undergoing an IVF cycle. INTERVENTION(S) Prospective evaluation of women with unoperated unilateral endometriomas undergoing IVF. The affected and contralateral intact gonads were compared in terms of responsiveness and oocyte quality. MAIN OUTCOME MEASURE(S) Oocyte developmental competence. RESULTS Ovarian responsiveness and oocyte quality did not significantly differ between the affected and intact gonads. The number of codominant follicles, the number of oocytes retrieved, and the number of suitable oocytes in affected and intact gonads were 3.7 ± 2.4 and 4.1 ± 1.7, 4.2 ± 3.1 and 4.7 ± 2.5, and 3.1 ± 2.6 and 3.5 ± 2.3, respectively. The number of viable embryos and the number of high-quality embryos were 1.8 ± 2.1 and 1.8 ± 1.4 and 1.0 ± 1.7 and 0.8 ± 0.7, respectively. The fertilization rate in the affected and intact gonads was 64% and 64%, respectively. The cleavage rate was 58% and 51%, respectively. The rate of high-quality embryos was 31% and 21%, respectively. CONCLUSION(S) In women undergoing IVF, the presence of ovarian endometriomas does not affect oocyte developmental competence.

The Rapid Growth of Fibroids during Early Pregnancy

Several studies aimed to disentangle whether pregnancy influences the growth of uterine fibroids but results were inconsistent. In this study, we speculated that fibroid enlargement during pregnancy may not be linear and we hypothesized that this phenomenon may mainly occur during initial pregnancy. To test this hypothesis, we set up a prospective cohort study of women with fibroids undergoing IVF. Cases were women achieving a viable pregnancy. Controls were the subsequent women with fibroids but failing to become pregnant. Twenty-five cases and 25 controls were recruited. The total number of fibroids in the two groups was 46 and 41, respectively. The mean ± SD diameter of the fibroids was 17±10 and 20±11 mm, respectively (p = 0.18). A statistically significant enlargement emerged exclusively in pregnant women. The median (Interquartile Range) modification of the diameter of the lesions in cases and controls was +34% (+6%/+65%) and +2% (−6%/+12%), respectively (p<0.001). The median (Interquartile Range) modification of the volume of the lesions was +140% (+23%/+357%) and 0% (−18%/+37%), respectively (p<0.001). In pregnant women, we failed to document any significant correlation between the magnitude of the growth and ovarian responsiveness to hyper-stimulation, suggesting that steroids hormones are not the unique factors involved. In conclusion, fibroids undergo a rapid and remarkable growth during initial pregnancy. Reasons behind this phenomenon remain to be clarified. The early rise in steroids hormones during early pregnancy may not be sufficient to explain the process. Other pregnancy-related hormones and proteins may play also key roles.

Age-related infertility and unexplained infertility: an intricate clinical dilemma

A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the womans age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed.

Serum anti-Müllerian hormone in subfertile women.

The correlation between ovarian reserve and infertility remains unclear. Albeit poorly predictive of pregnancy success in in vitro fertilization cycles, serum anti‐Müllerian hormone (AMH) has been acknowledged as a surrogate measure of ovarian reserve and is commonly evaluated in women seeking pregnancy. Disentangling whether low serum AMH affects natural fecundity is clinically important, as this information helps physicians in providing appropriate counseling to women and may impact on management strategies.

Fertility preservation in women with borderline ovarian tumours

Borderline ovarian tumours (BOT) may occur in young women and have an excellent survival rate. Therefore, there is the obligation to put emphasis on fertility preservation in affected women. On the other hand, it has also been underlined that the disease should be managed with caution because these tumours can relapse and, albeit rare, malignant transformation can also occur. Unfortunately, evidence on fertility preservation in women with BOT is scanty. In this opinion paper, we tried to draw some clinical indications based on the few available studies on the clinical management of BOT and their possible relation with controlled ovarian hyper-stimulation (COH). We ultimately came to the following conclusions: (1) Fertility counselling should become an integral part of the clinical management of women with BOT. Conservative management without pre-surgical counselling may expose women without reasonable chances of future conceptions to undue risks. (2) Despite some epidemiological concerns on the possible relation between COH and BOT, the conservative surgical treatment should be associated to oocyte cryopreservation considering the high risk of recurrence of the disease. (3) Letrozole during COH should be considered to temper the theoretical risk of increased recurrences. (4) Pregnancy should not be delayed in women at low-moderate risk of recurrences. Fertility preservation may be avoided in these women provided that they start active pregnancy seeking early. (5) Albeit experimental, oocytes retrieval from affected ovaries removed at the time of surgery can be considered. Conversely, ovarian cortex cryopreservation is not justified given the possible risks of malignant reseeding.

Risk of thrombosis in women with malignancies undergoing ovarian stimulation for fertility preservation

BACKGROUND Compared with the general population, cancer patients have a higher risk of venous thromboembolism as well as arterial thrombotic events such as stroke, myocardial infarction and peripheral arterial embolism. Therefore a possible concern for women with malignancies undergoing ovarian stimulation for fertility preservation is the increased risk of venous or arterial thrombosis. METHODS In this article, we revised current available literature on the risk of thrombosis in patients with cancer and in women undergoing ovarian stimulation, with the ultimate aim of drawing some indications for preventive measures. RESULTS Unfortunately, there are no specific data on the risk of thrombosis in women with cancer undergoing ovarian stimulation for fertility preservation. However, the literature suggests that the cancer type and stage, surgery, and chemotherapy all influence the risk of venous and, possibly, arterial thrombosis. Reports of cases of ovarian stimulation in women without malignancies have shown that venous thrombosis rarely occurs unless a pregnancy is achieved, while arterial thrombosis can occur in the absence of pregnancy but is usually only associated with ovarian hyperstimulation syndrome (OHSS). OHSS increases the risk of thrombotic events, but only the early form of the syndrome is relevant for women undergoing fertility preservation. CONCLUSIONS The available evidence on the risks of thrombosis for women undergoing ovarian stimulation for fertility preservation due to a malignancy is reassuring. However the avoidance of the early form of OHSS in women preserving oocytes/embryos due to malignancy is crucial. For these cycles, we advocate the use of a regimen of ovarian stimulation with gonadotrophin releasing hormone (GnRH) antagonists using GnRH agonists to trigger ovulation, an approach that has been shown to markedly reduce the risk of OHSS. Antithrombotic prophylaxis should be administered only to selected subgroups of women such as those with other risk factors or those who do develop early OHSS.

THE LONG-TERM IMPACT OF CONTROLLED OVARIAN HYPERSTIMULATION ON THYROID FUNCTION

OBJECTIVE Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle. METHODS Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH <2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4). RESULTS Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P<.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval [CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003). CONCLUSION COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.

Female fertility preserving practices at a pediatric unit: a challenge of multiprofessional and multidisciplinary cooperation.

Introduction Being able to have children could have an important positive effect on the future lives of pediatric cancer survivors. Working at a cancer institute makes us responsible for filling the gaps in our knowledge in this area of patient care. Methods We describe our activities in a series of young females diagnosed with cancer and evaluated for fertility preservation options. We discuss the developed skills and organization as well as the practical difficulties encountered in managing fertility preservation. Results Since September 2012, laparoscopy and cryopreservation of cortical ovarian tissue has been performed in 16 girls (with ovary transposition in 3, and after several cycles of chemotherapy in 5) and egg banking in 4 young women (before chemotherapy in 2 and several years after treatment in 2). Conclusions Recommendations on fertility preservation indicate that discussing the problems early on is crucial to future success. It is unthinkable to simply provide information and offer the opportunity to choose a fertility preserving technique without helping and accompanying patients and their families in their decisions and choices on the matter.