Exploring Attitudes to Conception in Partners and Young Women with Gynecologic Cancers Treated by Fertility Sparing Surgery.

BACKGROUND: Approximately 20% of women with gynecologic cancers are under age 40 and with delayed childbearing, women may be diagnosed before their first pregnancy. Although fertility preservation is a priority for many women, attitudes to conception have not previously been investigated in these patients or their partners. We explored attitudes to conception in partners and young women, following fertility preserving treatment for gynecologic cancers. METHODS: A total of 16 telephone interviews were conducted with a purposive sample of patients who had had an early stage gynecologic cancer or borderline ovarian tumor treated by fertility sparing surgery in Western Australia between January 1st, 2005 to December 31st, 2016. The interviews were audio recorded, transcribed and thematic analysis was conducted. RESULTS: Four main themes were identified: (i) Emotions at diagnosis and perception of information given; (ii) Discussions of fertility and factors affecting childbearing; (iii) Role of partners in decision making and relationship pressures; (iv) Decision for treatment and postoperative regrets. CONCLUSIONS: Regret and relationship breakdown were commonly reported. Women need appropriate support including inviting their partners to attend clinic appointments and may need several appointments before treatment. Regret was commonly reported by women who opted for completion surgery.
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Spontaneous Uterine Rupture in a Preterm Pregnancy following Myomectomy.

A 44-year-old nulliparous woman was transferred to a tertiary obstetric hospital for investigation of acute onset abdominal pain. She was at gestation of 32 weeks and 2 days with a history of previous laparoscopic fundal myomectomy. An initial bedside ultrasound demonstrated oligohydramnios. Following an episode of increased pain early the following morning, a formal ultrasound diagnosed a uterine rupture with the fetal arm extending through a uterine rent. An uncomplicated classical caesarean section was performed and the neonate was delivered in good condition but with a bruised and oedematous right arm. The neonate was transferred to the Special Care Nursery for neonatal care. The patient had an uncomplicated postoperative course and was discharged home three days following delivery. This is an unusual presentation of uterine rupture following myomectomy where the fetal arm had protruded through the uterine wall.

Maternal insulin-like growth factor 1 and 2 differentially affect the renin-angiotensin system during pregnancy in the guinea pig.

OBJECTIVE: Insulin-like growth factors (IGFs) are known to interact with the renin-angiotensin system (RAS). We previously demonstrated that administration of IGF1 to guinea pigs in early to mid pregnancy promotes placental function and fetal growth in mid to late gestation. Early administration of IGF2 had sustained, but not acute, effects on these parameters and also on placental structural differentiation. Here, we aimed to determine whether the IGFs interact with the placental RAS in early to mid gestation to modulate placental development and increase fetal growth and survival, and if IGF2 binding the IGF2R is implicated in the sustained effects of IGF2 treatment. DESIGN: At day 20 of pregnancy, guinea pigs were infused with 1m g/kg/day of IGF1, IGF2, (Leu27)IGF2 or vehicle for 18days and sacrificed on either day 62 (late pregnancy) or during the infusion period on day 35 (early-mid pregnancy). Placental structure at day 35 was analyzed using morphometric technique and expression of RAS genes in the placenta and placental and plasma renin activity were measured at both time points. RESULTS: Compared with vehicle at day 35 of gestation, IGF1 infusion reduced the total midsagittal cross-sectional area of the placenta (-17%, p = 0.02) and the labyrinth area (-22%, p = 0.014) but did not alter the labyrinth volume nor labyrinth:interlobium ratios. IGF2 treatment did not affect placental structure. IGF1 did not alter placental mRNA for any of the RAS genes quantified at day 35 (AGTR1, ACE, AGT, TGFB1) but increased TGFB1 expression by more than 16-fold (p = 0.005) at day 62. IGF2 increased placental expression of AGTR1 (+88%, p = 0.03) and decreased AGT (-73%, p = 0.01) compared with the vehicle-treated group at day 35, and both IGF2 and (Leu27)IGF2 increased expression of TGFB1 at day 62 by 9-fold (p = 0.016) and 6-fold (p = 0.019) respectively. Both IGFs increased the ratio of active:total placental renin protein (+22% p = 0.026 p = 0.038) compared to vehicle compared to vehicle at day 35 but not 62. At day 62, IGF2-treated mothers showed a marked increase in total plasma renin (+495%) and active renin (+359%) compared to vehicle but decreased the ratio of active to total renin by 41% (p = 0.042). (Leu27)IGF2-treated animals had higher levels of placental active renin (+73%, p = 0.001) and total renin (+71%, p = 0.001) compared with the vehicle control. CONCLUSIONS: The data obtained in the current study suggest the potential for alternate roles for the induction of the RAS after IGF treatment. IGF1 and 2 treatments increase the activation of prorenin to renin in the placenta, possibly due to increased protease activity. In addition, IGF2 treatment in early pregnancy may enhance the maternal adaptation to pregnancy through stimulation of renin in the kidney. The sustained effects on placental differentiation and function after IGF2 treatment suggest therapeutic potential for exogenous administration of IGFs in improving pregnancy outcomes.

Early pregnancy maternal endocrine insulin-like growth factor I programs the placenta for increased functional capacity throughout gestation.

In early pregnancy, the concentrations of IGFs increase in maternal blood. Treatment of pregnant guinea pigs with IGFs in early to midpregnancy enhances placental glucose transport and fetal growth and viability near term. In the current study, we determined whether exogenous IGFs altered placental gene expression, transport, and nutrient partitioning during treatment, which may then persist. Guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg x d) or vehicle sc from d 20-35 of pregnancy and killed on d 35 (term is 70 d) after administration of [(3)H]methyl-D-glucose (MG) and [(14)C]amino-isobutyric acid (AIB). IGF-I increased placental and fetal weights (+15 and +17%, respectively) and MG and AIB uptake by the placenta (+42 and +68%, respectively) and fetus (+59 and +90%, respectively). IGF-I increased placental mRNA expression of the amino acid transporter gene Slc38a2 (+780%) and reduced that of Igf2 (-51%), without altering the glucose transporter Slc2a1 or Vegf and Igf1 genes. There were modest effects of IGF-I treatment on MG and AIB uptake by individual maternal tissues and no effect on plasma glucose, total amino acids, free fatty acids, triglycerides, and cholesterol concentrations. IGF-II treatment of the mother did not alter any maternal, fetal or placental parameter. In conclusion, exogenous IGF-I, but not IGF-II, in early pregnancy increases placental transport of MG and AIB, enhancing midgestational fetal nutrient uptake and growth. This suggests that early pregnancy rises in maternal circulating IGF-I play a major role in regulating placental growth and functional development and thus fetal growth throughout gestation.

Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term.

Appropriate partitioning of nutrients between the mother and conceptus is a major determinant of pregnancy success, with placental transfer playing a key role. Insulin-like growth factors (IGFs) increase in the maternal circulation during early pregnancy and are predictive of fetal and placental growth. We have previously shown in the guinea pig that increasing maternal IGF abundance in early to midpregnancy enhances fetal growth and viability near term. We now show that this treatment promotes placental transport to the fetus, fetal substrate utilization, and nutrient partitioning near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg.kg-1.day-1) or vehicle subcutaneously from days 20-38 of pregnancy (term=69 days). Tissue uptake and placental transfer of the nonmetabolizable radio analogs [3H]methyl-D-glucose (MG) and [14C]aminoisobutyric acid (AIB) in vivo was measured on day 62. Early pregnancy exposure to elevated maternal IGF-I increased placental MG uptake by>70% (P=0.004), whereas each IGF increased fetal plasma MG concentrations by 40-50% (P<0.012). Both IGFs increased fetal tissue MG uptake (P<0.048), whereas IGF-I also increased AIB uptake by visceral organs (P=0.046). In the mother, earlier exposure to either IGF increased AIB uptake by visceral organs (P<0.014), whereas IGF-I also enhanced uptake of AIB by muscle (P=0.044) and MG uptake by visceral organs (P=0.016) and muscle (P=0.046). In conclusion, exogenous maternal IGFs in early pregnancy sustainedly increase maternal substrate utilization, placental transport of MG to the fetus, and fetal utilization of substrates near term. This was consistent with the previously observed increase in fetal growth and survival following IGF treatment.