Lars Nilsson

Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) would decrease hyperandrogenism and improve oligo/amenorrhea more effectively than physical exercise or no intervention. We randomized 84 women with PCOS, aged 18-37 yr, to 16 wk of low-frequency EA, physical exercise, or no intervention. The primary outcome measure changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography-mass spectrometry was analyzed by intention to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, and glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 wk of intervention, and after a 16-wk follow-up. After 16 wk of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α,17β-diol-3-glucuronide by -28% in the EA group (P = 0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P = 0.018 vs. exercise). After the 16-wk follow-up, the acne score decreased by -32% in the EA group (P = 0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-wk follow-up compared with no intervention. Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.

Fertilization and pregnancy after intracytoplasmic microinjection of acrosomeless spermatozoa

Spermatozoa lacking acrosomes were injected into the cytoplasm of mature human oocytes. In two subsequent cycles, 12 of 28 (43%) oocytes were fertilized, and the ET of the second cycle resulted in a twin pregnancy. This report describes, to the best of our knowledge, the first case of successful fertilization and delivery after using acrosomeless spermatozoa. Our hope is that with increasing experience with microinjection, in the near future, this type of infertility will not remain a serious problem.

The C. elegans P4-ATPase TAT-1 Regulates Lysosome Biogenesis and Endocytosis

P‐type adenosine triphosphatases (ATPases) of the Drs2p family (P4‐ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae, several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4‐ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)‐1 in intracellular trafficking. tat‐1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat‐1 loss‐of‐function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP‐1. In addition, they lack the same class of storage granules as lmp‐1 mutants, suggesting that part of the tat‐1 phenotype might result from LMP‐1 sequestration in an aberrant compartment. Epidermal cells mutant for tat‐1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT‐1 is required for yolk uptake in oocytes and an early step of fluid‐phase endocytosis in the intestine. Hence, TAT‐1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell‐specific effector proteins.

Caenorhabditis elegans num-1 negatively regulates endocytic recycling.

Much of the material taken into cells by endocytosis is rapidly returned to the plasma membrane by the endocytic recycling pathway. Although recycling is vital for the correct localization of cell membrane receptors and lipids, the molecular mechanisms that regulate recycling are only partially understood. Here we show that in Caenorhabditis elegans endocytic recycling is inhibited by NUM-1A, the nematode Numb homolog. NUM-1A∷GFP fusion protein is localized to the baso-lateral surfaces of many polarized epithelial cells, including the hypodermis and the intestine. We show that increased NUM-1A levels cause morphological defects in these cells similar to those caused by loss-of-function mutations in rme-1, a positive regulator of recycling in both C. elegans and mammals. We describe the isolation of worms lacking num-1A activity and show that, consistent with a model in which NUM-1A negatively regulates recycling in the intestine, loss of num-1A function bypasses the requirement for RME-1. Genetic epistasis analysis with rab-10, which is required at an early part of the recycling pathway, suggests that loss of num-1A function does not affect the uptake of material by endocytosis but rather inhibits baso-lateral recycling downstream of rab-10.

Couples' willingness to pay for IVF/ET

Acta Ohstet Gynecol Scand 1995; 74: 199–202.

The success rate in a Swedish in-vitro fertilization unit: a cohort study

Objective. To evaluate the cumulative childbirth rate after completion of in vitro fertilization (IVF) treatment including three or, in a few cases, four stimulated cycles. Design. A cohort of 398 couples starting their first IVF treatment between January 1990 and December 1992 were followed until completion of their treatment.

Preimplantation genetic diagnosis (PGD): The Gothenburg experience

Background. A program for preimplantation genetic diagnosis of pre‐embryos from patients with hereditary disorders was set up in our unit at Sahlgrenska University Hospital in 1994. The majority of the patients were carriers of X‐chromosome linked disorders; a few patients were translocation carriers. In this paper we describe our experiences of our first 36 cycles, 30 gender determinations and six analyses of embryos with possible translocations.

Cumulative birth rates following cryopreservation of all embryos in stimulatedin vitro fertilization (IVF) cycles

ObjectiveTo cryopreserve all good-quality embryos available after IVF is one way to avoid an impending hyperstimulation and a more attractive alternative to a couple than cancellation of the cycle. At Sahlgrenska University Hospital this method has been practiced since 1991. The aim of this study was to assess the success rate (defined as childbirth per couple) after IVF treatment including one stimulated cycle, resulting in cryopreservation of all good-quality embryos available, followed by replacement of frozen/thawed embryos in one or more natural cycles.DesignA cohort of 32 women undergoing one stimulation for IVF between January 1991 and December 1993 where all good-quality embryos were cryopreserved and transferred in a later spontaneous cycle were studied retrospectively. The cumulative childbirth rate per couple was calculated.ResultsA total of 28 women underwent a total of 45 transfers with frozen-thawed embryos. In 4 women no transfer has taken place so far. The clinical pregnancy rate per embryo transfer was 33% (15/45) and per patient 54% (15/28). Three spontaneous abortions occurred giving a cumulative childbirth rate per patient of 39% (11/ 28). In addition, 6 out of the 28 women still have embryos left in the freezer.ConclusionCryopreservation of all good-quality embryos available after IVF is a highly effective alternative to cancellation of a cycle when there is impending hyperstimulation. The use of this approach results in a cumulative childbirth rate per coupleof at least 39%. Since only one stimulation was performed, it also seems to be cost effective.

Caenorhabditis elegans Numb Inhibits Endocytic Recycling by Binding TAT-1 Aminophospholipid Translocase

Numb regulates endocytosis in many metazoans, but the mechanism by which it functions is not completely understood. Here we report that the Caenorhabditis elegans Numb ortholog, NUM‐1A, a regulator of endocytic recycling, binds the C isoform of transbilayer amphipath transporter‐1 (TAT‐1), a P4 family adenosine triphosphatase and putative aminophospholipid translocase that is required for proper endocytic trafficking. We demonstrate that TAT‐1 is differentially spliced during development and that TAT‐1C‐specific splicing occurs in the intestine where NUM‐1A is known to function. NUM‐1A and TAT‐1C colocalize in vivo. We have mapped the binding site to an NXXF motif in TAT‐1C. This motif is not required for TAT‐1C function but is required for NUM‐1As ability to inhibit recycling. We demonstrate that num‐1A and tat‐1 defects are both suppressed by the loss of the activity of PSSY‐1, a phosphatidylserine (PS) synthase. PS is mislocalized in intestinal cells with defects in tat‐1 or num‐1A function. We propose that NUM‐1A inhibits recycling by inhibiting TAT‐1Cs ability to translocate PS across the membranes of recycling endosomes.

Oocyte Retrieval under the Guidance of a Vaginal Transducer a

Ultrasound-guided ovum pick-up (OPU) is now an accepted technique in many human in vitro fertilization and embryo transfer ( IVF/ET) programs. To date, approximately 5000 pick-up procedures have been performed by ultrasound. The oocyte recovery rate varies between 5080% per punctured follicle. The pregnancy rate has been reported to be between 10-25%, which is the same as for groups where laparoscopy was used for the egg The technique used for OPU today does not affect the pregnancy rate, providing the method used results in as many mature and healthy oocytes as possible. The reason ultrasound-guided OPU was originally developed was that laparoscopy seemed to be too invasive a method to use when the only purpose was to obtain mature oocytes. Ultrasound-guided biopsy techniques are less invasive than other techniques used for puncture of intra-abdominal structures. Since diagnostic ultrasound has a long tradition among obstetricians and gynecologists, it is only natural that this technique was tried and later incorporated as a diagnostic and operative tool in IVF/ET programs. The main techniques used for ultrasound-guided OPU are transvesical*~ and perurethral.I4 However, both these methods of needle insertion have disadvantages, such as the need for rather heavy sedation of the patient. Furthermore, a prerequisite for both these puncturing routes is that the urinary bladder has to be full, a situation sometimes causing considerable discomfort to the patient. In addition, both methods require considerable training in ultrasound-guided puncture if they are to be successful and safe. With the knowledge that stimulated ovaries tend to be located deep in the pouch of Douglas, a technique was developed for puncturing follicles transvaginally under the guidance of abdominal ~canning.. ~ However, this technique still had some major disadvantages: It is a free-hand technique and the bladder has to be full. The intro-