Lyndon Hale

A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies.

OBJECTIVE To investigate whether heparin and low-dose aspirin increase the pregnancy rate in antiphospholipid antibody or antinuclear antibody-seropositive women with IVF implantation failure. DESIGN A double-blind, randomized, transfer-by-transfer of fresh or cryopreserved embryos, crossover trial.A hospital infertility clinic and associated IVF service. PATIENT(S) Women seropositive for at least one antiphospholipid (APA), antinuclear (ANA), or beta(2) glycoprotein I autoantibody and >or=10 embryos transferred without achieving pregnancy (n = 143). INTERVENTION(S) Subcutaneous unfractionated heparin (5000 IU b.i.d.) and aspirin (100 mg daily) (158 transfers of 296 embryos) or placebo (142 transfers of 259 embryos) from the day of embryo transfer. MAIN OUTCOME MEASURE(S) Fetal heart per embryo transferred (implantation rate). RESULT(S) There was no significant difference in pregnancy rates or implantation rates between treated and placebo cycles; for example, fetal hearts per embryo transferred implantation rates were 6.8% (20/296) and 8.5% (22/259), respectively, and the generalized estimating equation covariate adjusted relative pregnancy rate was 0.65 (95% confidence interval, 0.33-1.28). The implantation rate for seropositive trial participants (42/555, 7.6%) compared favorably with that for IVF implantation-failure patients continuing treatment outside the trial (147/3237, 4.5%). CONCLUSION(S) Heparin and aspirin did not improve pregnancy or implantation rates for APA-positive or ANA-positive patients with IVF implantation failure.

First reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy.

Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting.

Delivery of twins following heterotopic grafting of frozen-thawed ovarian tissue

Sir, We have recently published a case report in your journal (Stern et al., 2013) describing the first reported clinical pregnancy following heterotopic grafting of cryopreserved ovarian tissue in a woman after a bilateral oophorectomy. At the time of writing the article the patient had a 26-week intrauterine twin pregnancy and we would like to provide an update on the outcome of this pregnancy. As described, the patient had undergone oophorectomy for a granulosa cell tumour 9 years previously followed by prophylactic removal of the remaining ovary and subsequent ovarian tissue cryopreservation. After repeated assessments revealed no tumour recurrence, and no evidence of tumour in the stored tissue, she had frozen-thawed ovarian tissue grafted to the anterior abdominal wall on two occasions. There was no evidence of tumour seen at either laparoscopy. The patient underwent low-dose stimulation and in vitro fertilization resulting in two embryos which were transferred. Her pregnancy proceeded uneventfully apart from a brief admission at 26 weeks for threatened preterm labour and a shortened cervix, which remained stable. The patient subsequently had an elective lower segment Caesarean section at 37 weeks and delivered two healthy girls weighing 3320 and 3262 g. At operation there was macroscopic evidence of tumour involving the diaphragm and a peritoneal deposit at the left pelvic brim. There was no evidence of tumour in the graft sites. All macroscopic tumour was resected and histology confirmed granulosa cell tumour. Recurrent tumour development could be directly related to grafting of ovarian tissue. It could also be due to a recurrence of peritoneal deposits precipitated by the hormonal environment provided by a pregnancy, in a tumour known to be sensitive to hormonal stimulation. Whilst the absence of tumour extraperitoneally at or near the graft sites might support hormonal reactivation, we cannot exclude the possibility that tumour recurrence resulted from the grafted tissue. The patient will commence hormonal suppression with an aromatase inhibitor once breastfeeding is discontinued and a further laparoscopy is planned. While the prognosis for this patient remains excellent, this unfortunate outcome serves to remind us of the possibility of tumour cell transmission with grafting despite comprehensive prior histological and biochemical assessment.

The first Australian experience of heterotopic grafting of cryopreserved ovarian tissue: evidence of establishment of normal ovarian function.

Cryostorage of reproductive potential, in the form of ovarian cortex, for young women about to undergo cytotoxic therapies has been offered clinically for some time. However, the prospects of re‐establishing reproductive function using this tissue remain unclear. We now report reproducible follicular development, oocyte retrieval and embryo development following heterotopic grafting of cryopreserved ovarian cortex which had been stored for over 10 years.

Live birth following transfer of a cryopreserved embryo generated from a cryopreserved oocyte and a cryopreserved sperm: Case report

As is the case with non-frozen oocytes, the efficient and successful use of cryopreserved oocytes in human assisted reproduction is, in part, dependent on the ability to apply selection criteria when choosing the ‘best’ embryos for transfer from a cohort. In many cases this, in turn, will necessitate the cryopreservation of non-transferred embryos to minimise the risk of multiple pregnancy. It is therefore important to establish that an embryo, generated by fertilization of a frozen-thawed oocyte, can be capable of surviving subsequent cryopreservation while retaining the potential for normal development. In this case report, we document the delivery of a normal male infant following transfer of a frozen-thawed embryo, generated by the fertilization of a frozen-thawed oocyte by a frozen-thawed sperm.

Multiple deliveries: The reduced impact of in vitro fertilisation in Australia

The number of twins born in Australia steadily increased from 2420 sets in 1983 to 4458 sets in 2010. At one stage, almost 25% of all twin deliveries in Australia were a consequence of assisted reproductive technologies.

Assisted reproductive technology (ART) cumulative live birth rates following preimplantation genetic diagnosis for aneuploidy (PGD-A) or morphological assessment of embryos: A cohort analysis

Preimplantation genetic diagnosis for aneuploidy (PGD‐A) for all 24 chromosomes improves implantation and clinical pregnancy rates per single assisted reproductive technology (ART) cycle. However, there is limited data on the live‐birth rate of PGD‐A over repeated cycles.

Re: Replacement of one single embryo is just as successful as two embryo transfer, without the risk of multiple pregnancy

I wish to comment on the article written by Tong et al. titled: ‘Hysteroscopy under general anaesthesia, a near painless procedure’ in which they described having carried out a randomised, double-blind trial to investigate whether intrauterine lignocaine could decrease pain initiated by instrumentation. They have found out that for most women, hysteroscopy, dilatation and curettage causes either no pain or very little pain postoperatively. We have noticed that there is some paradoxical information given by the authors. In the ‘Introduction’ section they said that their experience had been that patients often complain of crampy abdominal pain afterwards, yet they have found that almost half of all women studied so far were completely pain free, with no difference between placebo and treatment groups. Of the remainder, most rated pain as ‘mild’ or less. I believe that their previous experience was not under general anaesthesia. If so, the study was performed in absence of considerable evidence that show patients who underwent hysteroscopy under general anaesthesia should experience postoperative crampy pain. In my opinion, before the current study, the authors should have carried out a study to elicit whether or not patients who underwent hysteroscopy under general anaesthesia experience any pain after the procedure. However, let me express my ideas regarding the use of local lignocaine application for patients undergoing hysteroscopy. Although we have not carried out such a study, according to our experience, patients who undergo hysteroscopy, endometrial sampling or other such intrauterine manipulations experience moderate postoperative campy pain, even when the procedure is performed under general anaesthesia. Recently we have carried out a study which measured the effect of intrauterine lignocaine gel application for hysterosalpingography (HSG) and found out that, despite the fact that lignocaine application had no value for pain experienced during HSG, it could eliminate post-HSG pain. In that case we speculated that pain after HSG may have a different mechanism and be related to prostaglandin production during instrumentation, which could be inhibited with local lignocaine application. Although we do not agree with Tong et al. we believe that their results are of interest and, if they are confirmed by other studies, speculation regarding an antiprostaglandin action of general anaesthetic agents may be appropriate.