Category Archives: Human Reproduction

BACKGROUND

The fifth leading cause of cancer deaths among women is ovarian cancer (OC), which originates primarily in the ovarian surface epithelium (OSE) that surrounds the ovary. Permanent removal of the OSE could provide a novel strategy to substantially reduce OC risk, while retaining the benefits of ovarian function, including gameto- and steroidogenesis. It must be determined whether ovarian surface epitheliectomy (OSEx) carries deleterious side effects, including loss of menstrual cyclicity, infertility or scarring (e.g. adhesions), prior to any clinical application of this strategy. To achieve this, we selected the non-human primate, rhesus macaque, for long-term (12 month) studies on the effects of OSEx.

METHODS

Rhesus macaque females underwent OSEx by detergent treatment and were then monitored for menstrual cyclicity (menstruation, steroidogenesis and follicle development) and adverse side effects (tissue scarring or adhesions). Ovaries were collected at 6 or 12 months and examined for evidence of tissue damage, follicle rupture and regression of the corpus luteum. The ovarian surface was examined immunohistologically for signs of epithelial replacement, using markers for OSE and fimbrial epithelium (FE), a possible alternative source of pelvic tumors diagnosed as OC.

RESULTS

After OSEx, menstrual cycle length, estrogen and progesterone production, follicle rupture and luteal regression appeared normal. No evidence of adhesions was seen. At 6 and 12 months post-OSEx, the ovarian surface was sparsely populated by cells expressing OSE and FE markers. Proliferative activity in this population was notably low.

CONCLUSIONS

OSEx may provide a novel method to reduce the risk of OC, without sacrificing ovarian function, although the effects on fertility remain to be tested. The absence of epithelial replacement via enhanced proliferation suggests OSEx does not increase malignant potential. Complete and permanent OSEx may be feasible.

BACKGROUND

Several studies have examined the relationship between direct antisperm antibody (ASA) levels in semen and pregnancy rate after advanced assisted reproductive technologies (ARTs) but the results have been inconsistent. The aim of our study was to further evaluate the relationship between ASA and pregnancy after IVF or ICSI by systematic review and meta-analysis.

METHODS

We conducted a systematic Medline search of all relevant full papers on direct semen ASA and pregnancy after IVF or ICSI. Three investigators independently reviewed the papers, followed by group discussion to choose the included papers. Meta-analysis was performed to get an odds ratio (OR) for the effect of ASA on pregnancy using IVF or ICSI.

RESULTS

The study identified and analyzed 16 valid studies (10 IVF and 6 ICSI). The study characteristics (including the ASA cutoff values) were heterogeneous. Our meta-analysis revealed that the combined OR for failure to achieve a pregnancy using IVF or ICSI in the presence of positive semen ASA was 1.22 (95% CI: 0.84, 1.77) and 1.00 (95% CI: 0.72, 1.38), respectively. The overall (IVF + ICSI) combined OR was 1.08 (95% CI: 0.85, 1.38).

CONCLUSION

This systematic review and meta-analysis indicate that semen antisperm antibodies are not related to pregnancy rates after IVF or ICSI, suggesting that both forms of ART remain viable options for infertile couples with semen ASA. However, additional, well-designed prospective studies using appropriate ASA cutoff levels are needed to further address this issue.

BACKGROUND

Epithelial ovarian cancer (EOC) risk correlates strongly with the number of ovulations that a woman experiences. The primary source of EOC in women is the ovarian surface epithelium (OSE). Mechanistic studies on the etiology of OSE transformation to EOC cannot be realistically performed in women. Selecting a suitable animal model to investigate the normal OSE in the context of ovulation should be guided by the model's reproductive similarities to women in natural features that are thought to contribute to EOC risk.

METHODS

We selected the non-human primate, rhesus macaque, as a surrogate to study the normal OSE during the natural menstrual cycle. We investigated OSE morphology and marker expression, plus cell proliferation and death in relation to menstrual cycle stage and ovulation.

RESULTS

OSE cells displayed a morphological range from squamous to columnar. Cycle-independent parameters and cycle-dependent changes were observed for OSE histology, steroid receptor expression, cell death, DNA repair and cell adhesion. Contrary to findings in non-primates, primate OSE cells were not manifestly cleared from the site of ovulation, nor were proliferation rates affected by ovulation or stage of the menstrual cycle. DNA repair proteins were more highly expressed in OSE than in other ovarian cells.

CONCLUSIONS

This study identifies significant differences between primate and non-primate OSE. In contrast to established views, ovulation-induced death and proliferation are not indicated as prominent contributors to EOC risk, but disruption of OSE cadherin-mediated adhesion may be, as could the loss of ovary-mediated chronic suppression of proliferation and elevation of DNA repair potential.

BACKGROUND

The impact of metabolic and reproductive features of polycystic ovary syndrome (PCOS) compromises psychological functioning. We investigated factors associated with negative psychological functioning to determine whether they were predictive of anxiety and depression in PCOS.

METHODS

A cross-sectional study was performed by questionnaire in 177 women with PCOS (mean ± SD age 32.8 ± 7.8 years) and 109 healthy controls (mean age 41.9 ± 15.4 years). Main outcome measures were anxiety and depression, measured using the Hospital Anxiety Depression Scale (HADS) and Multidimensional Body-Self Relations Questionnaire (MBSRQ), respectively.

RESULTS

Women with PCOS, compared with control women, had a higher mean anxiety HADS score (9.5 ± 3.9 versus 6.5 ± 3.6; P < 0.001), a higher mean depression score (5.7 ± 3.7 versus 3.3 ± 3.1; P < 0.001) and more negative body image in 7 out of 10 subscales of the MBSRQ. Multivariate regression analysis in PCOS showed that anxiety was predicted by self-worth (P < 0.0001), health evaluation (P = 0.005), time taken to diagnose PCOS (P = 0.003) and age (P = 0.02), while in control women, anxiety was predicted by self-worth (P = 0.009), health evaluation (P = 0.001) and rural living (P = 0.03). Depression in PCOS was predicted by self-worth (P = 0.0004), quality of life (QOL) (P = 0.004), fitness orientation (P = 0.002), appearance evaluation (P = 0.001) and time to diagnosis (P = 0.03) and in women without PCOS, by self-worth (P < 0.0001), QOL (P < 0.0001), illness orientation (P = 0.001) and appearance orientation (P = 0.02).

CONCLUSIONS

Women with PCOS have increased anxiety, depression and negative body image compared with women without PCOS. In women with or without PCOS, body image and self-worth are predictors of both anxiety and depression, while QOL also predicts only depression. Time taken to diagnose PCOS is associated with poor psychological functioning.

BACKGROUND

It is increasingly common for women in high-income countries to delay childbearing. We aimed to describe the context of pregnancy for first-time mothers of different ages and examine relationships among maternal age at first birth, mode of conception and psychosocial wellbeing in pregnancy.

METHODS

Using stratified sampling, we recruited similar numbers of women conceiving through assisted reproductive technology (ART; n = 297) or spontaneously (n = 295) across three age groups: younger, ≤20–30 years; middle, 31–36 years; older, ≥37 years. Women participated in a structured interview and completed validated questionnaires assessing socio-economic status, personality, quality of partner relationship, state and trait anxiety, pregnancy-focused (P-F) anxiety and maternal–fetal attachment.

RESULTS

Older maternal age was associated with lower depression and anxiety symptoms, lower maternal–fetal attachment (P< 0.05), greater psychological hardiness (resilience) (P< 0.001) and lower ratings of control in the partner relationship (P< 0.05) at a univariate level. ART conception, but not older maternal age, was associated with more P-F anxiety. Although most main effects of age and mode of conception became non-significant after controlling for contextual/reproductive history variables, a significant association between ART conception and more intense fetal attachment emerged (P< 0.05).

CONCLUSIONS

Women having their first baby when older appear to have some psychological advantages over their younger counterparts; they are more resilient, report their partners as less controlling and report lower symptoms of depression and anxiety during pregnancy. However, women conceiving through ART have a more complex experience of pregnancy, simultaneously experiencing more P-F anxiety and more intense emotional attachment to the fetus.

Aggressive chemotherapy generally results in the loss of both endocrine and reproductive functions. If the patient has not undergone previous oocyte, embryo or ovarian tissue cryopreservation, orthotopic allotransplantation of fresh ovarian tissue from a genetically non-identical sister may be considered. Here, we describe a case report. The patient, aged 15 years and presenting with homozygous sickle cell anemia, underwent chemotherapy (busulfan, cyclophosphamide) and total body irradiation before bone marrow transplantation, the donor being her HLA-compatible sister. HLA group analysis later revealed complete chimerism. When the patient was 32 years old, ovarian allografting was performed, with the ovarian tissue donor being the same sister who had already donated bone marrow. The goal was to restore ovarian activity and natural fertility. No immunosuppressive therapy was administered. No sign of rejection was observed. Restoration of ovarian function was achieved 3.5 months after transplantation, as proved by the first estradiol peak and follicular development detected by ultrasound. After 9 months of regular ovulatory cycles, IVF was attempted because proximal tubal stenosis (unknown at the time of grafting) could not be repaired by tubal reanastomosis. After stimulation, three oocytes were retrieved. Two embryos were obtained. One embryo was frozen and the other was transferred, resulting in an ongoing pregnancy. The patient delivered a healthy baby girl weighing 3.150 g at 37 2/7 weeks of gestation.